W1-1. Exosomal signalling in complications of pregnancy

45Abstracts for The 46th International Congress on Pathophysiology of Pregnancy

Workshop 1 Workshop 1

W1-1. Exosomal signalling in complications of pregnancy

Salomon C, Illanes, SE, Mitchell MD, Rice GEUniversity of Queensland Centre for Clinical Research, Australia

Complications of pregnancy are thought to be clinical manifestations of a common developmental lesion (i.e. inadequate invasion by extravillous trophoblast cells with a consequent failure to remodel maternal uterine spiral arteries). Available data support the hypothesis that dysfunctional exosomal signaling by placental cells contributes to this failure. Concomitant changes in the concentration of placental exosomes in pregnancies complicated by preeclampsia (PE), intrauterine growth restriction, preterm and gestational diabetes mellitus (GDM) may be prognostic and/or diagnostic of these complications. As such, the concentration, content and /or bioactivity of placenta-derived exosomes in maternal plasma may be informative of placental dysfunction. To test this hypothesis, placenta-derived exosomes present in maternal plasma during normal and complicated pregnancies (in this study, PE and GDM) were quantifi ed and characterised. Exosomes were isolated by differential and buoyant density centrifugation and characterised by nanoparticle tracking analysis, the expression of placenta and endosomal antigens, protein content and bioactivity. In normal pregnancies, the concentration, protein content and bioactivity of placenta-derived exosomes in maternal plasma varied signifi cantly with gestational age (p < 0.01). In pre-symptomatic GDM and PE pregnancies (< 20 weeks of gestation), the maternal plasma concentration of placenta-derived exosomes was more than two-fold that observed in controls. These data are consistent with the hypothesis that exosomes are released from the placenta during early pregnancy into maternal blood and may play a role in maternal adaptation to pregnancy. Gestational changes in the profi le and characteristics of exosomes in maternal blood may be of clinical utility in the diagnosis of placental dysfunction.

Brief Curriculum Vitae June 2014Professor Greg RicePhD, BSc, Master of Health Administration, Graduate Diploma of Management

Dr Rice is an NHMRC Principal Research Fellow, a Deputy Director of University of Queensland’s Centre for Clinical Research. He has broad-based experience in the biotechnology (both private and public), academic research and not-for-profi t organisations.Dr Rice was co-founder of private biotechnology company HealthLinx, (HTX, 2003) Executive Director (2006), General Manager Science and Operations (2007) and is the Chairman. The company listed on the ASX in 2006 as diagnostic company that focuses on the development and delivery of IVD MIAs. Dr Rice also severed as a member of Clinical and Scientifi c Advisory Committees of ASX-listed companies and is currently a member of the Technical and Regulatory Standing Committee of IVD Australia.Within the university and the public hospital sectors, Rice has extensive experience in basic and clinical research and has published over 220 peer-reviewed scientifi c publications. He has co-founded hospital-based, clinical research centres in both oncology and perinatology.Within the not-for-profi t sector, he has established public companies and as a founding director of these companies, implemented marketing and fund-raising programs to fund and develop medical research programs.

W1-2. Involvement of microRNAs in pathophysiology of preeclampsia

Toshihiro Takizawa1, Akihide Ohkuchi2, Shigeru Saito3, Toshiyuki Takeshita4

1Department of Molecular Medicine and Anatomy, and 4Department of Reproductive Medicine, Perinatology and Gynecologic Oncology, Nippon Medical School, Tokyo, Japan

2Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan 3Department of Obstetrics and Gynecology, University of Toyama, Toyama, Japan

MicroRNAs (miRNAs) are small noncoding RNAs that play important roles in regulating gene expression. MiRNAs within the miRNA cluster in human chromosome 19 are expressed exclusively in the placenta; i.e., placenta-specifi c miRNAs. We found that HSD17B1, the mRNA encoding hydroxysteroid (17-beta) dehydrogenase 1, a steroidogenetic enzyme expressed predominantly in the placenta, was downregulated by miR-210 and placenta-specifi c miRNA miR-518c that were aberrantly expressed in preeclamptic placenta. Furthermore, we showed that reducing plasma level of HSD17B1 preceded the onset of preeclampsia (PE). Our fi ndings reveal a novel mechanism of miRNAs underlying the molecular pathology of PE and identify a novel prognostic factor for PE.Placenta-specifi c miRNAs are not only expressed in the placenta but also secreted into the maternal circulation via exosomes. Although it is likely that exosomal placenta-specifi c miRNAs contribute to placenta-maternal cell communication, few studies have examined whether exosomal placenta-specifi c miRNAs modulate the expression of their targets in recipient maternal immune cells. As mentioned above, the increase of placenta-specifi c miR-518c expression dysregulated HSD17B1 gene expression in preeclamptic placenta. Similarly, placenta-specifi c miRNAs secreted form preeclamptic placenta may occur dysregulation of gene expression in maternal immune cells.

46 Abstracts for The 46th International Congress on Pathophysiology of Pregnancy

To address these questions, we are currently investigating the roles of exosomal placenta-specific miRNAs.

About My ResearchName: Toshihiro Takizawa

Present Address: Department of Molecular Medicine and Anatomy Nippon Medical School 1-1-5 Sendagi, Tokyo 113-8602, Japan

1986 MD, Jichi Medical School, Tochigi, Japan1994 PhD, Jichi Medical School, Tochigi, Japan

1986-1988 Resident, Jichi Medical School Hospital, Tochigi, Japan1988-1990 Surgeon, Iizuna Hospital, Nagano, Japan1994-2003 Assistant Professor at the Department of Anatomy, Jichi Medical School2001-2003 Visiting Scientist at the Department of Physiology and Cell Biology, the Ohio State University, Columbus, OH, USA, working under Professor John M. Robinson2003-present Professor at the Department of Molecular Medicine and Anatomy, Nippon Medical School, Tokyo, Japan

After studying on Fc gamma receptor on the human placenta as a visiting scientist at the Ohio State University (2001-2003), I came back to Tokyo, Japan and started studying microRNA in the human placenta. My research focuses on the biological functions of placenta-specific miRNAs.

W1-3. Biology and chemistry of a mouse model with pregnancy-associated hypertension

Akiyoshi FukamizuLife Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan

Pregnancy-induced hypertension (PIH) is a serious complication during pregnancy and characterized by elevated blood pressure in late pregnancy with severe peripheral tissue damage and high mortality in fetus suffering from intrauterine growth retardation. It is estimated to affect 5% of all pregnancy all over the world with severe aftermath on both maternal and fetal health. Recent epidemiological studies indicate the association between PIH and cardiac morbidity and mortality during the postpartum period. In the medical treatment for chronic hypertension in non-pregnant state, angiotensin receptor blocker and angiotensin converting enzyme inhibitor are recommended as first-line therapy, but both are forbidden for female patients in pre- and post-partum periods due to possibility of fetal and neonatal abnormalities. Therefore, as a genetically engineered model animal, I will discuss the application of pregnancy-associated hypertensive mice.

Akiyoshi FUKAMIZU, Ph.D.Professor and Vice DirectorLife Science Center, Tsukuba Advanced Research Alliance,University of Tsukuba,Education:1982-1983 Faculty of Agricultural and Forestry, University of Tsukuba: Awarded the B.S. degree.1984-1986 Master’s Degree Program in Environmental Sciences, University of Tsukuba: Awarded the M.S. degree.1986-1987 Doctoral Degree Program in Agricultural Science, University of Tsukuba.1989 Awarded the Ph.D. degree (University of Tsukuba).Professionals:1994-1995 Research Associate at the Salk Institute for Biological Studies, USA.1996-1998 Associate Professor at the Institute of Applied Biochemistry, University of Tsukuba1999-2012 Professor, Center for Tsukuba Advanced Research Alliance (TARA), University of Tsukuba2002-2006 Program Leader in The 21st Century COE Program (Life Science), MEXT, Japan2011- Program Leader in Scientific Research on Innovative Areas “Transcription and Metabolism”2011- Professor and Vice Director, Life Science Center, TARA, University of TsukubaEditors:1997- International Journal of Molecular Medicine (Editorial Academy)2002- Journal of Receptors and Signal Transduction (Asian Editor-in-Chief)2005-2008 Endocrinology (Editorial Board)2005-2008 Hypertension Research (Editorial Board Member)2005-2007 Journal of Biochemistry (Editorial Board Member)


2009- Heart and Vessels (Associate Editor)2014- Molecular and Cellular Biology (Editorial Board)Awards:1993 Young Investigator’s Award from Japan Vascular Disease Research Foundation.1993 Nikkei BP Award (Medical Science Aspect) from Nikkei Business Publication.1996 Tsukuba Prize from Ibaraki Science and Technology Foundation.1996 Young Investigator’s Award from the Japanese Society of Biochemistry.1997 Jokichi Takamine Young Investigator’s Award from the Japanese Society of Cardiovascular and Endocrinological

Metabolism.

W1-4. Exploration of preeclampsia model mice

Keiichi Kumasawa Department of Obstetrics and and Gynecology, Osaka University, Japan

Introduction: Preeclampsia is diagnosed by hypertension and proteinuria in pregnant women. When it becomes severe, it is threatening to both mothers and fetuses. It affects about 5% of pregnant women, and about 16% of maternal death were due to hypertensive disorders including preeclampsia. Thus far fundamental management is termination of pregnancy, and it comes to increase preterm births. Though this syndrome is reported from the ancient, for example Hippocrates’ book and a lot of researches have been done, the exact cause of preeclampsia is still unknown. It is partly because of the lack of appropriate model animals. Some animal models were produced by the systemic expression of sFLT1, but it did not reflect the fact that preeclampsia was due to some troubles in placenta.Methods: Thus far we explored placental specific lentiviral genetic transduction to mice, and this time we applied the way to make a more physiological model mice of preeclampsia. This time we focused on human soluble VEGF recepter1(hsFLT1)which was reported to be related with systemic symptom.Results: HsFLT1 overexpressing placentas led dams increasing blood pressure from E16.5 and proteinuria at E18.5. And both symptom disappeared after delivery, which mimicked human cases.Conclusions: We succeeded in making more physiologically preeclamptic model mice. And these mice can be suitable for exploration of therapy of preeclampsia.

Brief sketch of my careerLast academic career2010 Graduation of Ph.D course in Department of Obstetrics and Gynecology, Osaka University, Osaka, JapanProfessional Training and Employment2002 Resident, Department of Obstetrics and Gynecology, Osaka University Hospital, Osaka, Japan2003 Resident, Department of Obstetrics and Gynecology, Mino City Hospital, Osaka, Japan2005 Senior resident, Department of Obstetrics and Gynecology, Osaka University Hospital, Osaka, Japan2010 Clinical fellow in Department of Obstetrics and Gynecology, Suita City Hospital, Osaka, Japan2011 Assistant professor in Department of Obstetrics and Gynecology, Osaka University Hospital, Osaka, JapanLicence2002 Medical Doctor’s License, Japan2007 Medical Specialist of Obstetrics and GynecologyAward2010 Excellent Presentation Award in Internationl Symposium for Reproductive Immunology (Containing Japan Symposium for

Reproductive Immunology)2011 Excellent Presentation award in the 21st Annual Meeting of The Society of the Kidney and pregnancy2012 Award of excellent paper presented by Japan Society of Obstetrics and Gynecology

W1-5. Pathogenesis of preeclampsia: COMT deficiency and its relevance.

Keizo KanasakiDepartment of Diabetology and Endocrinology, Kanazawa Medical University

Preeclampsia is a devastating pregnancy-associated hypertensive syndrome. Although it is quite common, the pathophysiology of preeclampsia is not yet clear, and it remains “the disease of theory”. We have been analyzing the relevance of catechol metabolism defect by catechol-o-methyltransferase (COMT) deficiency in the pathomechanisms of preeclampsia. We already showed that pregnant COMT deficient mice exhibited preeclampsia like phenotype; 2-methoxyestradiol, the estradiol metabolite via COMT, would rescue the


preeclampsia like phenotype by the restoration of placental oxygen status. Most of clinical analyze by others have been supported that COMT defi cient theory would be relevant for the pathogenesis of preeclampsia. Although convincing, we still need to demonstrate whether COMT defi ciency could explain key symptoms in preeclampsia. First, we analyzed the hypertension associated with COMT defi ciency is caused by relevant pathophysiological mechanisms as reported in preeclampsia. Regard with this, preeclampsia has been associated with hypersensitivity against vasoactive peptide. Second, we focused on glucose tolerance defects observed in preeclampsia and analyzed whether such glucose tolerance defects are explained by COMT defi ciency. In my talk, I would like to discuss about the working hypothesis about COMT defi ciency and preeclampsia including preliminary data obtained to support much deeper relevance of COMT defi ciency on preeclampsia pathogenesis.

CVDr. Keizo Kanasaki graduated with his MD (1996)/PhD (2003) from Shiga University of Medical Sciences, Japan. From 2005 he joined Prof. Raghu Kalluri’s lab, Division of Matrix Biology, Beth Israel Deaconess Medical Center, in Harvard Medical School as a post-doctoral fellow; from 2008 to 2010, he promoted as Instructor. In Kalluri lab, he established fi rst genetic mouse model of preeclampsia, COMT defi cient mice (2008). From 2010, he got assistant professor position at Department of Diabetology and Endocrinology, Kanazawa Medical University, Japan and he was promoted as senior assistant professor in same year. In Kanazawa Medical University he has been investigating molecular connections between preeclampsia and metabolic syndromes. He was awarded a visiting professorship at Luzhou Medical College, Sichuan, China in 2011. He obtained Scientifi c Award of the “Society for the Study of the Kidney in Pregnancy” in 2012 (Japan).


W2-1. Rising prevalence of GDM in India – Challenges and opportunities

Hema DivakarImmediate past President FOGSI - India

There is overwhelming evidence of the magnitude of GDM in countries of South Asia. There is clear and adequate evidence that the magnitude of GDM in these countries is at a level that needs a holistic public health approach for appropriate intervention, in the form of universal screening of pregnant women.Variance in incidence have been reported in various literature, and this variance can be explained by the different methods and criteria used for diagnosis; There has been a signifi cant increase in the trend of prevalence of GDM over the past three decades, reaching to as high as 21% in some parts of India. But it is evident that the problem is a signifi cant one that needs programmatic intervention. Advocacy need to be directed to policy makers, programme managers, clinicians including obstetricians, and other health care providers. Women and the community are to be made aware and this should lead to demand generation, by which pregnant women will request to be tested for GDM. A strong message should also be communicated on the economic and development perspective that underscores the ‘invest in women’ message.

Mothers and diabetes is one of WDF’s eight focus areas. Focusing on gestational diabetes is a low-cost intervention both to improve maternal and child health but also to prevent future diabetes. Providing screening and care to mothers at risk of gestational diabetes is likely to have a multi-generational impact on the benefi ciaries as well as on health care systems and budgets.The talk will deliberate on issues revolving aroundDiffi culties when conducting screening for GDM and how to overcome themManagement of GDM, including diet, exercise and insulinImplications of uncontrolled/undiagnosed GDM on the mother and foetus/childUsage of glucometer / Importance of follow up during pregnancy /ReferralMotivation and education of mothers about screening, treatment and follow upObstetrical management in diabetes and pregnancy/Perinatal monitoring

Dr Hema DivakarGraduated and postgraduated in Mumbai & now a leading Obgyn in Bengaluru, Karnataka and hon visiting prof. at Kuppam medical college

Qualifi cationsDGO 1986 – (Mumbai) • MD 1989-Wadia MaternityHospital (Mumbai)• FICMCH 1999-(Calcutta) FICOG 2000 - (Mumbai) FRCOG 2014• Postgraduate diploma in Medical Law & Ethics• Diploma from All IndiaInstitute of Management• Masters Degree in AlternativeMedicine


• PG Diploma in Preventive &Promotive Health Care

Established “DIVAKARS SPECIALITY HOSPITAL” in 1990 in Bengaluru,Area of interest High Risk Pregnancy Care.

Organisational positions heldPresident FOGSI 2013 – national body of 30,000 obgyns as members on rollHon Secretary of ICOG 2009 – 2011 – head of academic councilSenior Vice President, FOGSI 2005•Chairperson Perinatology Committee, FOGSI 2003•National Editorial board FOGSI Journal.•

Activities with GOVERNMENT of India(1) Emergency Obstetric care programme• Contributed in the capacity of National technical expert• Director for standards and quality control• Monitoring and evaluation• Training and supportive supervision for medical officers in rural India(2) Technical expert on the hospital accreditation committee for improving standards of health care delivery systems(3) Head of research projects in Rural India on issues related to: Anemia in Pregnancy /HIV AIDS• /Contraception• Postpartum depression Diabetes in pregnancy•

W2-2. Screening and managing diabetes in pregnancy : “The Italian Model”

Battini Lorella1, Lacaria Emilia2, Trojano Giuseppe1, Bottone Pietro1,

Fulceri Marco Anselmo, Carmignani Arianna1, Cattani Raffaella1, Salerno Maria Giovanna1, Del Prato Stefano2, Di Cianni Graziano3,

Bertolotto Alessandra2

1Dept. Obstetrics-Gynaecology 2nd Unit, University-HealthCare System, Pisa, Italy 2Dept. Endocrinology and Metabolism, University of Pisa, Italy

3C.O.U. Diabetology and Metabolism Diseases, Sanitary Local Unit, Livorno, Italy

Diabetes complicates about 3-10% of all pregnancies, with sensible variability related to racial differences. Frequency has significantly increased in last decades, with double rate incidence in all ethnical groups. In Italy, diabetes affecting pregnancies, according to ADA criteria before 2010, reaches 8-9% prevalence, and about 10% in migrating women.Diabetes and abnormal glucose metabolism during pregnancy may be pre-existing (diabetes type 1, 2, impaired glucose tolerance) or occur during pregnancy ( gestational diabetes ).To reduce maternal-fetal morbidity/mortality careful pregnancy planning for pregestational diabetes and early identification for gestational diabetes are fundamental.Gestational diabetes (GDM) screening is still controversial. In March 2010, the IADPSG criteria for GDM was accepted by Italian Consensus Conference. Comparing estimates of GDM prevalence, calculated by new and old diagnostic criteria, among Italian population, a strongly significant increase in gestational diabetes prevalence emerges ( + 136.8%), which decreases when results are compared to different historic categories of impaired gestational glucose metabolism ( + 33.8%). Since 2011, screening has been restricted from universal to selected on the basis of low, medium and high risk factors for GDM.The “ Italian Model ” evolution of screening and managing diabetes in pregnancy and its impact will be addressed and discussed.

Prof/Dr Lorella Battini DM,PhDAcademician Secretary of IAMSS OGASHVice President of World OGASH Board (elect)Chairperson of Presidium IAMSSHonorary Consultant to OGASH Academy - CSPPProfessor of OGASH

GENERAL COORDINATOR OF OGASH INSTITUTIONSCONTINENTAL (EUROPE) CHAIRMAN OF OGASHDEVELOPER OF POSTGRADUATE COURSE PROJECT OGASHWEB OGASH ECM Educational Program

WINNER OF PROF. IOSEB JORDANIA INTERNATIONAL PRIZE - 2008WINNER OF ERNST THEODOR RIPPMANN MEDAL DE ONOARE 2009POST-GRADUATE ADVANCED COURSE ON DIABETES AND PREGNANCYPisa, Italy, February 22-23, 2008, Chairmen: G. Di Cianni, S. Del Prato

SIGO 2009International Special Symposium “SIGO for Organisation Gestosis and OGASH”:


Celebration the OG 40th Jubilee ProgramNominant of World Health Summit, Berlin,2009

DEVELOPER OF POSTGRADUATE COURSE PROJECT OGASH

Member of the New York Academy of Sciences Developer of OGASH on the etiopathological role of HLA-DR in Gestosis Syndrome (Rippmann’s Syndrome)

[CERTIFICATE OF ELECTION] [CERTIFICATE OF ELECTION] [CERTIFICATE OF ELECTION]Tel/Fax: 0039 0587 420279Cell-Phone: 333/7997070E-mail: [email protected]

OGASH IAMSS WEB LIBRARY GOLDEN ARCHIVE of PISA UNIVERSITYE-mail: [email protected]

Presentations:

information fromOGASH IAMSS WEB LIBRARY GOLDEN ARCHIVE of PISA UNIVERSITYE-mail: [email protected]

GENERAL COORDINATOR OF OGASH INSTITUTIONSCONTINENTAL (EUROPE) CHAIRMAN OF OGASHVice President of World OGASH BoardChairperson of Presidium IAMSSProf/Dr Lorella Battini DM,PhD

Prof Ferdinando Brunori Memorial Celebration Promoter of HLA-DR studies on Etyopathogenesis of EPH Gestosis

Honorary Academician of OGASHPresident of IAMSSPRIZE-WINNER OF HERA’s GOLDEN PRIZE 2005-2006 click hereModerator of Special Symposium OGASH – Intercontinental Society for the Study of GestosisIntercontinental Academy of Medical-Social Sciences (IAMSS) CME Credits.Photo

Florence 2006

GUEST EDITORDr. Lorella Battini MD.COORDINATOR OF OGASH SPECIAL SESSIONGENERAL COORDINATOR OF OGASH INSTITUTIONSCorrespondent member of IAMSSAwarded Presentations

See Archive: 1 2OGASH ProfessorsCOMMISSION MEMBERS OF IAMSS CME (Photo)

[RADIOLOGY]

The Interventional Radiology ServiceUltrasound Education and Research Centre вЂњGEOJEFF”ВќDiRECTOR PROF. MALKHAZ MIZANDARI

[DIABETES AND PREGNANCY]

DIABETES & GESTOSISEuropean Board of Diabetes and Endocrine Associations ofIntercontinental OGASH Academy

Pisa, 22-23 Febbraio 2008POST-GRADUATE ADVANCED COURSE on DIABETES AND PREGNANCY

Prof/Dr Lorella Battini DM,PhDOGASH IAMSS WEB LIBRARY GOLDEN ARCHIVE DIRECTOR of PISA UNIVERSITYE-mail: [email protected] about:

ENDOCRINOLOGY DEPARTMENTIntercontinental Academy of Medical-Social Sciences (IAMSS)


W2-3. Clinical features of gestational diabetes mellitus by the new consensus criteria: Three year experience in a single institution in Japan.

Kei MiyakoshiDepartment of Obstetrics and Gynecology, School of Medicine, Keio University

There is a paucity of information on perinatal data regarding gestational diabetes mellitus (GDM) by the new criteria from a real experience because the number of healthcare associations implementing the criteria is still limited. In Japan, the new recommendation was adopted in 2010, and is commonly used in the obstetric practice. In our hospital, women with GDM underwent self-monitoring of blood glucose measurements as well as dietary management. Additionally, insulin treatment was initiated when dietary treatment did not achieve the glycemic goal. Using a cohort of women with singleton pregnancy receiving perinatal care at our hospital between 2011 and 2013, clinical features of new criteria-defined GDM were reviewed. The incidence of GDM was 14%, mainly by one abnormal OGTT value (1-AV). GDM women with 1-AV showed less severe glucose intolerance than those with two or three abnormal OGTT values, but appeared at high risk of insulin requirement when a family history of diabetes existed. When compared perinatal outcomes between women with normal glucose tolerance and GDM, fetal growth were comparable between the two groups. Medical intervention for women with new criteria-defined GDM could contribute to the improvement of pregnancy outcomes, although further studies on the clinical and cost-effective management are needed. Our data would be useful for healthcare professionals considering the new criteria.

Curriculum Vitae3/1992 MD, School of Medicine, Keio University6/1992-6/1998 Residency, Obstetrics and Gynecology School of Medicine, Keio University7/1998-6/2001 Clinical fellow, Tokyo Dental College, Ichikawa General Hospital7/2001-3/2004 Instructor, School of Medicine, Keio University4/2004- 12/2006 Research fellow, Oregon National Primate Research Center1/2007-6/2008 Clinical fellow, Saitama City Hospital7/2008-9/2009 Instructor, School of Medicine, Keio University10/2009-present Assistant Professor, School of Medicine, Keio University

W2-4. Management for mild gestational diabetes in Japan: messages from a retrospective multi-institutional study

Takashi SugiyamaDepartment of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine

In 2010, the criteria for diagnosing GDM proposed by the IADPSG were adopted in Japan. The frequency of GDM consequently increased 2 to 4 fold as compared with the previous criteria. Among women with newly-diagnosed GDM, most had only one abnormal value (OAV) based on the previous criteria. A multi-institutional retrospective review was thus performed by the Japan GDM Study Group to assess whether the treatment of mild GDM, i.e., one abnormal 75-g OGTT value, improves pregnancy outcomes in Japan.In a multi-institutional retrospective study, we examined pregnant women meeting the criteria for mild GDM (i.e., OAV for 75-g OGTT; fasting glucose ≥ 100 mg/dL, 1-h postprandial glucose ≥ 180 mg/dL, and 2-h postprandial glucose ≥ 150 mg/dL), receiving either routine prenatal care (non-treatment group: 542 women) or dietary intervention alone or dietary intervention with self-monitoring of blood glucose and/or insulin therapy, if necessary (treatment group: 351 women). Pregnancy outcomes were compared between these groups.Multiple logistic regression analysis (MLRA) revealed that pre-pregnancy BMI and gestational weight gain were associated with LGA infants, while 75-g OGTT results were unrelated to LGA. When overweight and obese women were the subjects, the number of LGA infants was significantly lower in the intervention than in the control group, and gestational weight gain was significantly lower in the treatment than in the control group. MLRA showed that intervention was significantly related to a lower incidence of LGA infants.This study suggests that maternal BMI impacts fetal growth and that treatment for overweight or obese mothers with OAV is associated with a lower frequency of LGA infants.

Education:1993 Ph. D. (Dr. of Medical Science), Mie University Graduate School of Medicine1988 M.D. Kansai Medical University SchoolProfessional Training and Employment:2013-present Professor in the Division of Maternal and Fetal Perinatal Medicine of Tohoku University Hospital2012-2013 Associate Professor in the Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine2002-2012 Associate Professor in Division of Maternal and Fetal Perinatal Medicine of Mie University Hospital2001-2002 Assistant Professor in the Department of Obstetrics and Gynecology, Mie University School of Medicine, Mie, Japan


2000-2001 Department of Obstetrics, Osaka Medical Center and Research Institute for Maternal and Child Health1998-2000 Assistant Professor in the Department of Obstetrics and Gynecology, Mie University School of Medicine1995-1998 Postdoctoral Fellow in the Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center1994-1995 Assistant Professor in the Department of Obstetrics and Gynecology, Mie University School of Medicine1988-1990 Resident in the Department of Obstetrics and Gynecology, Mie University School of Medicine

W2-5. Adipocytokines in gestational diabetes mellitus and offspring’s metabolic syndrome

Hisashi Masuyama, Yuji HiramatsuDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

Normal pregnancy is characterized by insulin resistance, which contributes to development of gestational diabetes mellitus (GDM) and preeclampsia. Obesity is one of risk factors for GDM and preeclampsia, while dysregulation of adipocytokines, such as leptin and adiponectin, due to obesity cause abnormal glucose and lipid metabolism and insulin resistance. In addition, obesity and insulin resistance in the mother might play a direct role in the transmission of an obesogenic and diabetogenic trait from generation to generation, but the role of genes and a shared environment are not completely understood. We demonstrated that adiponectin level and insulin sensitivity were significantly decreased in GDM patients compared with normal glucose tolerance in obese women. Minor alterations in angiogenic factor concentrations, elevated insulin resistance and mildly elevated adiponectin level may be involved in the pathophysiology of late-onset preeclampsia in obese patients. We also observed that a high fat diet (HFD) induced obesity in pregnant mice resulted in hypertension, proteinuria, and macrosomia with insulin resistance and abnormal adipocytokine levels and that the exposure to an HFD in utero might lead to a metabolic syndrome-like phenomenon through epigenetic modifications of the genes encoding adipocytokines, adiponectin and leptin in the offspring.These data suggested that adipocytokines might play important roles in pathophysiology of GDM and late-onset preeclampsia in obese women and in the origin of metabolic syndrome in adulthood of offspring.

Hisashi Masuyama, MD, Ph. D.Associate Professor, Department of Obstetrics and Gynecology, Okayama University GraduateSchool of Medicine, Dentistry and Pharmaceutical Sciences

Education;1991-1995 Ph.D. Okayama University Graduate School of Medicine1987-1991 Clinical training1981-1987 M.D. Okayama University Medical SchoolAppointments2012-present Associate Professor, Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine,

Dentistry and Pharmaceutical Sciences2008-2012 Associate Professor, Perinatal center, Okayama University Hospital2006-2008 Assistant Professor, Department of Obstetrics and Gynecology, Okayama University Hospital2000-2001 Research fellow in Case Western Reserve University, Ohio, USA, supported by the research program from the Ministry

of Education, Culture, Sports, Science and Technology of Japan1999-2006 Instructor, Department of Obstetrics and Gynecology, Okayama University Hospital1997-1999 Medical staff, Department of Obstetrics and Gynecology, Okayama University Hospital1995-1997 Postdoctoral Fellow, Department of Pharmacology and Physiological Science, St. Louis University, St. Louis, Missouri, USAAwards2005 Okayama Medical Association Award (Yuki Award)2004 Okayama University Medical Award (Hayashibara Award)2004 Yagi Memorial Award (The Chugoku and Shikoku Society of Obstetrics and Gynecology)2001 Young Investigator Award (The Endocrine Society’s 83rd Annual Meeting, Denver, USA)1997 Young Investigator Award (10th Workshop on Vitamin D, Strasbourg, France)



W3-1. Endothelial dysfunction in the pathogenesis of preeclampsia

Keiichi MatsubaraDepartment of Obstetrics and Gynecology, Ehime University School of Medicine

Early in pregnancy, abundant neovascularization at the implantation site is important for normal placentation, so that suffi cient nutrients and oxygen can reach the fetus. For placental development and reduction of uterine vascular resistance, cytotrophoblasts must migrate to the decidua and the uterine myometrium, with subsequent invasion of the spiral arteries. Cytotrophoblasts replace the endothelium in the spiral arteries, reduce vascular resistance, and increase the blood supply to the fetus. However, in preeclampsia, the reconstitution of spiral arteries does not extend to the myometrium, which leads to poor placentation, defi cient fetal blood supply, placental ischemia, and fetal growth restriction. The resulting increased peripheral vascular resistance leads to maternal hypertension. The vascular dysfunction is mediated by the imbalance of serum factors including nitric oxide and reactive oxygen species, angiotensin II receptor subtype 1 and subtype 2, etc. The imbalance is deeply involved in the pathophysiology of preeclampsia through the endothelial dysfunction.

Curriculum VitaePersonal Data:

Name: Keiichi MatsubaraAddress: Department of Obstetrics and Gynecology, Ehime University School of MedicineShizukawa, Toon, Ehime, 791-0295,

JapanEducation:

1988 M.D., Ehime University School of Medicine1994 Ph.D., Ehime University Postgraduate School of Medicine

Professional Training and Employment:2012-present Associate Professor in the Department of Obstetrics and Gynecology, Ehime University2011-2012 Department Director in the Department of Obstetrics and Gynecology, NTT west Matsuyama Hospital2010-2011 Department Director in the Department of Obstetrics and Gynecology, Ehime Prefectural Central Hospital2005-2010 Associate Professor in the Department of Obstetrics and Gynecology, Ehime University2001-2002 Visiting Assistant Professor, Department of Obstetrics & Gynecology, Perinatal Research Laboratories, University of

Wisconsin-Madison1998-2005 Assistant Professor in the Department of Obstetrics and Gynecology, Ehime University1996-1998 Assistant in the Department of Obstetrics and Gynecology, Ehime University

Awards:2005 Asia Oceania Federation of Obstetrics & Gynecology Young Scientist Award

W3-2. Lysophosphatidic acid signaling as a functional modulator of trophoblasts and its relevance to the pathology of preeclampsia

Takeshi Nagamatsu, Mayuko Ichikawa, Yuki Kawai-Iwasawa, Tatsuya Fujii,Kei Kawana, Takahiro Yamashita, Tomoyuki Fujii

Department of Obstetrics and Gynecology, The University of Tokyo

Lysophosphatidic acid (LPA) is a novel lipid mediator produced mediated by enzymatic action of a secretary peptide, autotaxin (ATX). In past works, LPA receptor 3 (LPAR3) is localized to reproductive organs and gene deletion mice have demonstrated a critical role of LPA-LPA3R axis in implantation. This study aimed to examine the involvement of LPA:LPAR3 signaling in the regulation of trophoblast cell function. The association of this signaling pathway with the etiology of preeclampsia (PE) was also investigated.Immunohistochemical staining of human placenta indicated a constant ATX production in all trophoblast types, whereas LPAR3 expression was limited to differentiated trophoblast population including extra-villous trophoblasts and syncytiotrophoblast. The alteration in gene expression profi le in LPAR3-transfected HTR8/SVneo upon a stimulation with a specifi c agonist, T13 was performed using DNA array analysis. LPAR3 stimulation evoked up-regulation of the expression for gene groups related to eicosanoid synthesis, cell differentiation and cytokines/chemokines which were reported to play signifi cant roles in fetomaternal immunity. These observations imply that LPA:LPAR3 axis controls trophoblast activities, consequently leading to healthy placentation.In the analysis on the peripheral blood from women with PE, reduced ATX concentration was observed prior to the manifestation of clinical symptoms. ATX mRNA level was lower in preeclamptic placentas compared with normal placentas. Interestingly, the degree of ATX mRNA reduction was more remarkable in early onset type than in late onset type. Considering the close link of impaired placental formation with early onset type, the aberrant function of LPA signaling might be one of pathogenic factors for PE.


BiographyTakeshi Nagamatsu, MD, PhDJob title; LecturerAffiliation; Department of Obstetrics and Gynecology, the University of Tokyo

Background;Mar. 1999 Graduated from Faculty of Medicine, University of Tokyo.Qualified as a medical doctor.Apr. 1999-Sep. 2000Completed the residency course at Tokyo University Hospital.Apr. 2002-Mar. 2006Research work targeting fetomaternal immune regulation and placental angiogenesis.Completed doctoral course and received PhD degree in Faculty of Medicine, University of Tokyo. Jan.2008-Mar.2010Postdoctoral fellow in University of Missouri.Research project targeting co-stimulatory signaling at the fetomaternal interface.Apr. 2010-Jan.2014Assistant professor in department of OB/GYN in the University of Tokyo.Feb. 2014-presentLecturer in Department of OB/GYN in the University of Tokyo.Chief physician in obstetric ward.

W3-3. Adipocytokine and inflammation in preeclampsia

Katsuhiko NaruseObstetrics & Gynecology, Nara Medical University, Kashihara, Nara Japan

Inflammation and insulin resistance in pregnancy are mainly produced by placenta and adipose tissue. The pathological change of preeclampsia (PE) is manifested on third trimester of pregnancy, after the increase in physiological load of pregnancy on the basis of early placentation failure. Most of the cytokines derived from adipose tissue (adipocytokines) were similarly altered in the patients with a normal pregnancy course and PE. However, chemokine MCP-1 level was decreased in the normal pregnancy group but increased in the PE, indicating the adipocytokine-induced pathological inflammation in PE. We also performed novel culture method of adipose tissue with or without serum samples from PE patients, and performed PCR array of inflammatory genes. Altered genes were related to chemokine and toll-like receptor (“homeostatic inflammation”), which plays a central role in systemic inflammation of PE.We also measured RAGE (receptor for advanced glycation endproducts)-ligands, a major “Danger Signal” in the human body. Levels of HMGB1 and S100A12 were increased in patients with PE. Especially, an increase in HMGB1 level may support the 2-step theory, that the molecule is regarded as a surface marker of trophoblast-derived “microparticles”. Pathological mechanism of PE may include both placentation failure and inflammatory response of adipose tissue.

Curriculum vitaeKatsuhiko Naruse, Nara Medical University, Japan

Katsu Naruse, born 1973, is an assistant professor and obstetrician-in-chief of Nara Medical University (NMU) Hospital, a perinatal emergency center for over 10,000 prefectural births per year. He graduated School of Medicine, NMU and obtained MD in 1999 and Post-graduate School, NMU and obtained PhD in 2005. From 2005 to 2007, he researched into early human placentation in Institute of Cellular Medicine, Newcastle University, UK, and since 2007, he back in NMU for basic research, obstetrical emergency including preeclampsia or postpartum hemorrhage, and notably, teaching activity for students same time. Beside of his busy clinical works as board certified members of JSOG / JSPNM / JSUM / JBMG, he is one of the most well-known researching obstetrician of the generation, especially for adipocytokine, metabolism and inflammation in preeclampsia, or proteinase activities in early placentation, and has been awarded as a young researcher in ISSHP (2004, 2006, 2008), IFPA (2006, 2007), JSSHP (2007), JSOG (2008) and Nara Prefectural Medical Association (2010), and is invited for symposium talk opportunity in FIGO (2006) and JSOG (2013). He published or supervised over 20 research and clinical manuscripts, and also works as society organizers, such as vice secretary-general of JSSHP or a councilor of JSPNM.


W3-4. Angiogenic factors in preeclampsia

Kaori KogaObstetrics and Gynecology, the University of Tokyo, Japan

Soluble fms-like tyrosine kinase 1 (sFlt1) is a splice variant of Flt1, acts as a potent antagonist for vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). We found that the level of sFlt1 in serum from women with preeclampsia was ~ > 6-fold higher than that from control. This may point to an involvement of sFlt1 in the pathophysiology of preeclampsia possibly by antagonizing of VEGF/PlGF effects on the formation of placental vasculature and maternal endothelial cell function (Koga et al 2003). Furthermore, we and other groups demonstrated that the elevation of serum sFlt1 preceded the manifestation of preeclampsia, which suggests a potential of this molecule as a diagnostic marker.Serum sFlt1 levels were also shown to be elevated in conditions that may predispose mothers to preeclampsia, such as a twin pregnancy and certain viral infections. We have demonstrated that sera from patients with hydatidiform mole, a condition also known to cause severe preeclampsia in early pregnancy, contain high level of sFlt1, and the level decreases markedly after the evacuation of molar tissue (Koga et al 2010). These findings imply that serum sFlt1 is derived from the placenta and sFlt1 may cause preeclamptic symptom despite the absence of fetus.We will also introduce factors that may up-regulate sFlt1 expression in trophoblasts, such as hypoxia and thrombin (Zhao et al 2012). These understanding may contribute to the development of novel strategies for prevention/ treatment of this dysfunction.

Dr Kaori Koga received her MD from Chiba University in 1996 and PhD from the University of Tokyo in 2003. She completed her residency in Ob/Gyn in Tokyo and Ibaraki, followed by a fellowship in the University of Tokyo. Dr Koga qualified as an Ob/Gyn doctor in 2001 and then as a certified reproductive medicine specialist, and a certified gynecological laparoscopist in 2011. She undertook post-doctoral fellowships in the Uterine Biology Group led by Prof. Lois Salamonsen at Prince Henry’s Institute, Melbourne, Australia in 2006, and the Reproductive Immunology Unit at the Department of Obstetrics, Gynecology and Reproductive Sciences, led by Prof. Gil Mor in Yale University in 2007-8.Dr Koga has received awards for her research from the Tokyo medical association (2002), the Japan Society for the Study of TOXEMIA OF PREGNANCY (2003), the Japan Society of Gynecologic and Obstetric Endoscopy (2005), and the American society for reproductive immunology (2008).Dr Koga is currently an Ob/Gyn assistant professor at the University of Tokyo, Japan. Her clinical interests include endometriosis, infertility and laparoscopic surgery, and her research interests include embryo implantation, feto-maternal interaction, and etiology of endometriosis, implantation failure and preeclampsia.

W3-5. Management preeclampsia

Gus Dekker

University of Adelaide, Australia

Preeclampsia is a progressive disorder that will inevitably worsen if pregnancy continues. Current therapy does not ameliorate the placental pathology nor alter the pathophysiology or natural history of preeclampsia. Delivery is the definitive management and is followed by resolution, generally over a few days but sometimes much longer. At mature gestational age (37 weeks and more), delivery should not be delayed. Even so, it is important to control severe hypertension and other maternal derangements before subjecting the woman to the stresses of delivery. Prolongation of pregnancy in the presence of preeclampsia carries no benefit for the mother but is desirable at early gestations to improve the fetal prognosis as in general, fetal outcome is proportional to gestational age at delivery. In cases of preterm preeclampsia before 34 weeks, delivery should be delayed for at least 24-48 hours if maternal and fetal status permit, to allow fetal benefit from antenatal corticosteroids administered for lung maturation. A number of trials have shown that 25-30% of women managed expectantly with preeclampsia will develop severe morbidity including HELLP syndrome, abruption, pulmonary edema and eclampsia and that the mean duration of prolongation is less than 12 days. It should be noted that this rate of complications also exists in patient managed with prompt delivery. Continuation also carries fetal risk and some stillbirths will occur despite careful monitoring.The management of women with preeclampsia between gestational ages of 24-32 weeks should be restricted to those centres with appropriate experience and expertise. Clear “endpoints” for delivery should be defined for each patient such that the decision to terminate the pregnancy is based on agreed criteria. In many cases, the timing of delivery will be based upon a number of factors, maternal and/or fetal rather than a single absolute indication for delivery. For preeclampsia prior to 24 weeks gestation, termination of pregnancy is almost universally the best option.

　(CV, P. 29)



W4-1. PPH – Lessons from confi dential inquiries – thoughts for the future

S. ArulkumaranProfessor Emeritus, St George’s University of London, England

The stepwise rapid succession of medical followed by surgical interventions can stop or minimize the bleeding and correct the blood loss and prevent the cascade of events that lead to massive blood loss, hysterectomy, admission to ICU and deaths. ‘Too little, too late’ has been highlighted in successive confi dential enquiries into maternal deaths in the UK. The phenomenon of ‘too little, too late’ can be tackled by the use of the mnemonic ‘HAEMOSTASIS’.H - Ask for HelpA - Assess (vital parameters, blood loss) and ResuscitateE - Establish etiology, Ensure availability of blood. EcbolicsM - Massage Uterus – bimanual compressionO - Oxytocin infusion / prostaglandins -S - Shift to theatre – to exclude retained products and trauma/ bimanual compression/ Antishock garment/ Aortic compressionT - Tamponade – Balloon / uterine packing / tranexamic acid - exclude ‘tissue and tears’A - Apply compression sutures –S - Systematic Pelvic devascularisationI - Interventional - Uterine artery embolisationS - Subtotal / Total abdominal hysterectomyGive oxygen, adequate fl uids, blood and blood products. No response to oxytocin or, ergometrine warrants infusion of oxytocin to keep the uterus contracted to allow clotting of uterine vessels. Next step is bimanual uterine massage and prostaglandins (parenteral PGF or misoprosotol PG E1 orally or sublingually -600 micrograms). Blood loss could be about 70 ml/min when the uterus relaxes and hence a 14 Gauge needle to give fl uids rapidly should be used X 2 lines. Tranexamic acid 1-2 gm intravenously, an antithrombolytic prevents the clot from lysing. An antishock garment which squeezes the blood into the circulation and also has a compressive effect on the uterus could be tried. Consumptive coagulopathy, lack of clotting factors, activation of fi brinolysis, large volumes of fl uids, metabolic acidosis and hypothermia aggravates the situation and is controlled by fi brinogen and clotting factors. Shock is proportionate to blood loss - mild 15%, moderate 30%, and severe 45%. Transfusion of one unit packed red blood cells to unit plasma as opposed to four packed cells to one unit plasma results in a 60 to 70% reduction in mortality in war injury victims -same principle after blood loss of > 2L of blood loss is useful. Freeze dried fi brinogen concentrate that can be reconstituted may be an alternative. Platelet transfusion may be needed but this is rare. Failure to arrest haemorrhage by medical therapy should be followed by a ‘Tamponade Test’. It will only work when there is no coagulopathy. Sengstaken, Rusche, Cooke’s catheter or condom or rubber glove tied to a plastic catheter can be inserted into the uterus and fi lled with warm saline/ water bleeding completely stops. If bleeding stops the balloon can be taken out in 6 hours. Patient should have broad spectrum antibiotics and an oxytocin infusion. Vital parameters, fundal height and bleeding per vagina should be monitored. If the test is going to be effective it will be known within 5 minutes. If the tamponade fails to stop the bleeding, a laparotomy should be performed and compression sutures (B- lynch or 2 to 5 vertical) should be employed. Failure of compression sutures should lead to systematic devascularisation by tying the infundibulopelvic and uterine vessels and/or anterior branch of the internal iliacs. Arterial embolisation using radiological guidance can be tried where facilities exist. Failure to arrest haemorrhage or deterioration of general condition of the patient should prompt sub-total or total hysterectomy.

　(CV, P. 27)

W4-2. Massive primary postpartum hemorrhage: embolization or hysterectomy?

Jin-Chung ShihDepartment of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan

Postpartum hemorrhage (PPH) due to various etiologies, including uterine atony and abnormal placentation, represents the most common cause of maternal mortality in the developed world. Traditional management consists of peripartum hysterectomy, selective hypogastric artery ligation, and more conservative approaches such pharmaceutical and uterine embolization have also been advocated recently. Substandard care and ‘too little being done too late’ remain a signifi cant debate between different series. For massive primary PPH, should


we go straightforward to hysterectomy? Some authors may think embolization should be considered as the first choice? There is no consensus at current era. In this brief talk, I try to review the existing literature and compare the efficacy and complications of these two procedures.The authors may favor hysterectomy as the first priority for PPH mainly because of the rich collateral of blood supply to the uteus. The hemostasis effect of emboliation for placenta accreta cannot sustain a long period. Besides, a number of complications (such as bladder ischemia, thrombosis) result from embolization were ever reported. These efficacy/complications distract the routine use of uterine embolization as the first line treatment of PPH.However, surgical intervention for massive primary PPH needs a detailed preparation of surgery, including instrument and transfusion. Besides, hysterectomy needs a carefully dissection of adjacent organs (such as bladder and bowel), which may result in more severe surgical complications than PPH itself. Finally, continuous bleeding from the wound of hysterectomy due to placenta accreta is usually substantial. Based on these reasons, some authorities do not favor hysterectomy as the line treatment for massive primary PPH.

　(CV, P. 30)

W4-3. Usefulness of balloon tamponade and compression suture for massive uterine bleeding

Shintaro MakinoJuntendo University

Objective: Various surgical hemostatic methods for postpartum hemorrhage have been reported. The aim of this study was to evaluate the usefulness of balloon tamponade and compression sutures for controlling uterine bleeding. Methods: We analyzed 146 patients who showed massive uterine bleeding (vaginal delivery > 1,000mL (n = 26), cesarean delivery > 2,000mL (n = 120)) about hemostatic methods and their prognosis. Hemostatic methods include bimanual compression, additional oxytocin injection, balloon tamponade, compression sutures, transcatheter arterial embolization (TAE) and hysterectomy. Results: Balloon tamponade was employed for 12 cases after vaginal delivery and TAE was performed for 1 case who was diagnosed as failure of balloon tamponade. Vertical compression sutures were used in 7 cases and 1 of these cases needed additional suture of uterine body because of atonic bleeding. In this case, hysterectomy was performed because of failure of compression suture.Conclusions: The balloon tamponade and vertical compression suture are simple, easy, and effective for controlling bleeding in women with PPH. We now believe that these technique should be performed to avoid excess TAE or hysterectomy. Subsequent menstruation resume and pregnancy will also be discussed in this presentation.

CURRICULUM VITAEShintaro MakinoEducation: 1995-2001 Juntendo University School of MedicineDegree: 2001 M.D. Juntendo University Faculty of Medicine 2006 PhD Juntendo UniversityMedical License: 2001 JapanProfessional Training and Employment:

2014- Department manager, department of obstetrics and gynecology, Juntendo Hospital2012- Associate professor, department of obstetrics and gynecology, Juntendo Hospital2011- Chief of Obstetrics, Juntendo Hospital2005- 2006 Research fellow in Perinatal research centre, University of Alberta2003- 2005 Senior Resident in Obstetrics and Gynecology, Juntendo hospital2002- 2003 Medical stuff in Obstetrics and Gynecology, Saitama Medical Center2001- 2002 Junior resident in Obstetrics and Gynecology, Juntendo Hospital

Specialty Board Certification:Board certified member, Japan Society of Obstetrics and GynecologyBoard certified member, Japan Society of Perinatal and Neonatal Medicine

Societies:• Society for Gynecologic Investigations• Japan Society of Obstetrics and Gynecology• The Japan Society of Ultrasonic in Medicine• Japan Society of Perinatal and Neonatal Medicine• The Japan Society for the Study of Hypertension in Pregnancy• International Society for the Study of Hypertension in Pregnancy• International Federation of Placental Association• Japan Federation of Placental Association• Asia and Oceania Federation of Obstetrics and Gynaecology• World Congress of Perinatal Medicine


W4-4. Management of postpartum hemorrhage

Eiji KondohAssociate Professor, Department of Gynecology and Obstetrics, Kyoto University, Graduate School of Medicine, Kyoto 606-8507, Japan

Postpartum hemorrhage (PPH) is one of the leading causes of maternal morbidity and mortality worldwide. The causes of PPH include uterine atony, genital tract lacerations, and placenta previa. When PPH persists despite conventional conservative treatments, we sometimes face difficult decisions on whether and to what extent hemostatic interventions (e.g. intrauterine balloon tamponade, radiological intervention, and hysterectomy) should be conducted. Here, I would like to introduce treatment decision-making for PPH using dynamic CT, and how we have improved the success rate of intrauterine balloon tamponade.Placenta previa accreta (PPA) is a potentially life-threatening obstetric condition, and has become increasingly common with the rising rate of cesarean deliveries. Conservative management, leaving the placenta behind, has gradually been accepted because it can reduce hemorrhage, preserve fertility, and prevent damage to the surrounding tissue. I will show that intrauterine balloon tamponade can be a useful addition to the options for the conservative management of PPA when partial detachment of the placenta causes intraoperative massive hemorrhage. Moreover, I present a complete observational cohort of every attempted case of conservative management in our institution. In each case the placenta vanished spontaneously and none of the patients required hysterectomy. Serial alterations in the placenta and its blood flow will be demonstrated using ultrasonography and dynamic MRI along with monitoring of serum beta hCG levels in the postpartum period.

Eiji Kondoh, MD, PhDAssociate Professor, Department of Gynecology and ObstetricsKyoto University Graduate School of MedicineKyoto 606-8507, Japan

1998 MD, Kyoto University Faculty of Medicine2007-2009 Visiting Scholar at Duke University2009 PhD, Kyoto University Graduate School of Medicine2009 Assistant Professor, Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine2011-2013 Chief of Obstetric and Delivery Care Unit at Kyoto University Hospital2013 Associate Professor and Principal Investigator, Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine

Research interests: postpartum hemorrhage, preeclampsia

W4-5. Management of Coagulopathy (Obstetrical DIC)

Atsuo ItakuraDepartment of Obstetrics and Gynecology, Juntendo University

Postpartum hemorrhage (PPH) often complicates dilutional or consumptive coagulopathy (obstetrical DIC), and obstetrical DIC may lead to life-threatening uterine or microvascular bleeding. Substitution with blood products containing coagulation factors is necessary for managing such patients. Although substitution of fibrinogen concentrate (FC) or cryoprecipitate is the standard treatment for obstetrical DIC in several developed countries, fresh frozen plasma (FFP) transfusion still has been used as the standard treatment for microvascular bleeding in Japan. So we have administered off-label FC for obstetrical DIC cases. To assess the efficacy and safety of FC in the treatment of obstetrical DIC, we reviewed medical records (2006-2011) of such cases. The overall response to FC was considered good in 12 cases, moderate in 4, and poor in 2. Fibrinogen levels significantly increased after FC substitution (approximately 40 mg/L/g FC). No serious adverse events were causally associated with FC substitution therapy. Then we created a new transfusion protocol for obstetrical DIC, in which FC and FFP are administered according to PT% and plasma fibrinogen value. We evaluated the usefulness of our protocol by comparing the prognosis of obstetrical DIC patients before and after the implementation of the protocol. FFP transfusion amount, FFP/RCC ratio, and mean blood loss were reduced significantly after the introduction of the protocol. There were no adverse events associated with the protocol. Our transfusion protocol, taking priority of FC, is effective and safe for the treatment of obstetrical DIC.

CURRICULUM VITAEAtsuo ItakuraProfessor of Obstetrics and GynecologyJuntendo University

Mailing Address:Department of Obstetrics and Gynecology tel: 81-3-5802-1100 Ex 3367


Juntendo University fax: 81-3-5689-74602-1-1 Hongo, Bunkyo-kuTokyo, Japan

e-mail [email protected]

Education:Ph.D. (Medical) Nagoya University, 2000 (Major fi eld: Obstetrics)

Dissertation: Human amniotic fl uid motogenic activity for fetal alveolar type II cells by way of hepatocyte growth factor. Obstet Gynecol 1997; 89: 729-733

Graduation (Medical) Nagoya University School of Medicine, 1986Current Academic Position

Professor, Department of Obstetrics and Gynecology, Juntendo UniversityVisiting Professor, Department of Obstetrics and Gynecology Saitama Medical University

Other Current Professional PositionsBoard Members, Japan Society of Obstetrical, Gynecological & Neonatal HematologyBoard Members, The Japanese Society of Diabetes and Pregnancy.Board Members, Japan Society for the study of Hypertension in Pregnancy.Councilor, Japan Society of Perinatal and Neonatal Medicine.Editor in Chief, Journal of Japan Society of Obstetrical, Gynecological & Neonatal Hematology.Associate Editor, Journal of Obstetrics and Gynecology Research

Previous Administrative Positions Held:2008-2013: Assistant Directors, Saitama Medical University Hospital2008-2013: Chair, Center for Child Health and Development, Saitama Medical University

HospitalPrevious Academic Positions Held:

2006-2013: Professor, Obstetrics and Gynecology, Saitama Medical University2002-2005: Associate Professor, Maternal and Perinatal Care Center, Nagoya University Hospital1994-2002: Assistant Professor, Nagoya University Hospital

Research and Publications: Journals and BooksJournal articles:

Author and co-author 212 original scientifi c papers, reviews, and chapter in books.


W5-1. Incidence of eclampsia in Japanese women

Kazushi Watanabe1, Yoshikatsu Suzuki2, Tamao Yamamoto3

1Department of Obstetrics and Gynecology, Aichi Medical University School of Medicine, Aichi, Japan2Department of Obstetrics and Gynecology, Nagoya City West Medical Center, Aichi, Japan

3Department of Obstetrics and Gynecology, Nagoya City University, Aichi, Japan

Aim: The aim of this study was to assess the rate of eclampsia in Japanese women and the relationship between changes in blood pressure (BP) and eclamptic episode.Methods: We used the perinatal database of the Japan Society of Obstetrics and Gynecology to access 330,399 deliveries after 22 weeks of gestation across 125 centers of the perinatal network between 2005 and 2009. A total of 246 women with eclampsia were identifi ed. The main outcome measures used were incidence, maternal age, body mass index (BMI), parity, gestational age at delivery, and mortality rate. We retrospectively investigated the severity of BP elevation just before eclamptic episode.Results: We identifi ed a total of 246 cases of eclampsia which corresponded to an incidence of 7.4/10,000 deliveries with a mean age of onset of 30.7 ± 5.8 years. The proportion of primiparous women was 81.3%, and the mean gestational age at delivery was 36.7 ± 4.0 weeks. Four maternal deaths were identifi ed. Systolic BPs just before eclamptic episodes in 11 eclamptic patients were160 mmHg or more.Conclusions: The rate of eclampsia in Japanese women was 7.4/10,000 deliveries. The risk of eclamptic episode may be higher in 160 mmHg or more of systolic BP.

CURRICULUM VITAEName Kazushi WatanabeSex MaleCitizenship JapanPosition Associate Professor Department of Obstetrics and Gynecology


Perinatal and Neonatal Medical Center Aichi Medical University School of MedicineMailing Address Department of Obstetrics and Gynecology Aichi Medical University School Nagakute-city, Aichi, Japan 480-1195 Phone: + 81-561-62-3311 Fax: + 81-561-62-2991 e-mail: [email protected] [email protected] of birth 18 September, 1964Education

1985-1991 Kochi Medical School of Medicine (Kochi Japan)2000 Awarded the degree of Doctor of Philosophy

Occupation1992 Resident1994 Research associate1995 Assistant professor

Department of Obstetrics and Gynecology Kochi Medical School of Medicine2004 Assistant professor Department of Obstetrics and Gynecology Kochi Medical University School of medicine2006 Lecturer Department of Obstetrics and Gynecology Aichi Medical University School of medicine2009-present Associate Professor

Department of Obstetrics and GynecologyPerinatal and Neonatal Medical CenterAichi Medical University School of Medicine

Societies Japan Society of Obstetrics and Gynecology Japan Society for the Study of Hypertension IN Pregnancy (Officer in chief) Japan Society for Perinatal and Neonatol Medicine

W5-2. Management of eclampsia and stroke during pregnancy

Yasumasa OhnoOhno Ladies Clinic

Eclampsia and stroke during pregnancy are major causes of maternal and neonatal death. To establish the etiologies and therapeutic strategies for the eclampsia and stroke during pregnancy, we performed a questionnaire based study in Aichi prefecture.This study revealed the following findings: 66% of deliveries were managed in primary medical institutions, 38% of eclampsia and 39% of stroke occurred at primary medical institutions, and 26% of stroke occurred at home.We investigated cases of eclampsia and/or stroke during pregnancy and revealed important issues regarding their management. In case with eclampsia, accurate antihypertensive and anticonvulsive treatment are necessary. Discriminating between eclampsia and stroke is difficult. However, when unconsciousness, facial muscle weakness, arm muscle weakness or a facial deficit is detected, stroke should be suspected. Brain CT can detected most of hemorrhagic strokes. When a stroke is detected, collaborative treatment with neurosurgeons should be started. If stroke is suspected at a primary medical institution, rapid maternal transport to an intensive medical institution is necessary. In patient whose blood pressure is greater than 180/120mmHg, the reduction of their blood pressure should be performed rapidly.These findings might aid the development of therapeutic strategies for pregnant women with eclampsia or stroke.

CURRICULUM VITAEName: Yasumasa OhnoDate of Birth: 24 March 1962Present Address: 10 Takahata, Inari-cho, 482-0012 Iwakura-city, Aichi, JapanEducationUndergraduate:

1981-1987 Kazawa University School of Medicine, Awarded the M.D.Graduated:

1990-1993 Nagoya University School of Medicine, Awarded the Ph.D.Professional Background

1994-1998 Medical stuff in Obstetrics and Gynecology, Toyohashi Municipal Hospital, Toyohashi, Japan1998-1999 “Post Vert” of INSERM Unit-99, Creteil, France2000-2004 Assistant Professor in Obstetrics and Gynecology, Nagoya University Hospital, Nagoya, Japan


2004-present Director of Ohno Ladies Clinic, Aichi, Japan2005-present Lecturer, Nagoya University School of Medicine, Nagoya, Japan

Membership of Academic SocietiesJapan Society of Obstetrics and Gynecology (Member of perinatal committee and guideline making committee)Japan Society of Perinatal and Neonatal Medicine (Councilor)Japan Society for the Study of Hypertension in Pregnancy (Board of director)

AwardsSilver medal of 1st International Conference of Perinatal Medicine (1991)Chairman’s award of Japanese Public Health Association (2013)

W5-3. Determination of antithrombin activity (AT) enhances “Safety” of the management of pregnant women, especially in women with multifetal pregnancies, hypertension, proteinuria, or edema

Hisanori Minakami, Mamoru Morikawa, Takahiro Yamada, Rina AkaishiDepartment of Obstetrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan

Monitoring of platelet counts helps to identify early women with at higher risk of HELLP syndrome. However, some women with liver dysfunction similar to the HELLP syndrome do not exhibit thrombocytopnenia, but almost all of such women exhibit pregnancy-induced AT deficiency (PIATD) defined as a gradual decrease in AT activity until the time of delivery, with AT activity reaching < 65% of the normal activity level. These women are diagnosed clinically as having acute fatty liver of pregnancy (AFLP).Although PIATD is likely to occur in women with hypertensive disorders including gestational hypertension and preeclampsia (approximately 20% and 1.0% for women with and without hypertension, respectively), it occurs frequently and independently of hypertension in multifetal pregnancies (10%, and 40% for twin and triplet pregnancies, respectively). This explains why women with multifetal pregnancies are likely to develop AFLP. The PIATD is also likely to occur in the absence of hypertension in women with isolated proteinuria or isolated edema. Ascites frequently seen in patients with preeclampsia contains abundant AT, suggesting that AT escapes from the blood into the interstitial space in the presence of an increased vascular permeability. Women with PIATD show a large and sustained decrease in the hematocrit value after delivery irrespective of the presence or absence of hypertension, suggesting a severe antenatal hemoconcentration and a decrease in the plasma volume in women with PIATD. Thus, AT activity in obstetrical practice enhances the “safety” of the management of pregnant women.

Brief CVHisanori Minakami, MD, PhD, Director Professor, Department of Obstetrics, Hokkaido University Graduate School of Medicine since 2001. After graduation from Gunma University School of Medicine in 1976, he worked for Jichi Medical School as an obstetrician gynecologist. He was promoted to an associate professor, Department of Obstetrics and Gynecology, Jichi Medical School in 1996.

W5-4. Emergency Critical care in pregnant women in India

Girija Wagh

Obstetrics and Gynecology at the Bharati Vidyapeeth University Medical College at Pune, India

Emergency Critical care in India is oft necessary in the context of hypertensive disorders in Pregnancy (HDP) especially eclampsia and Hemorrhagic problems such as antepartum and postpartum hemorrhage. Atonic postpartum hemorrhage continues to be a serious problem. So does eclampsia and other complications of HDP. Anemia is an important background risk which aggravates the situation. Uterine inversion, fulminant liver diseases, ARDS, rupture uterus due to misoprostol use are some other causesEctopic pregnancies too are on the rise. Fetal emergencies such as bradycardia, obstructed labour cordprolapse, preterm delivery too are common.The country still battles with a high maternal mortality and morbidity though many measures have been undertaken by the government, the private sector and organizations such as the FOGSI

Professor Girija Wagh currently is the Head of the Obstetrics and Gynecology at the Bharati Vidyapeeth University Medical College at Pune, India, MCI recognized institution and NAAC reaccredited Grade A university. She is the Member of the Scientific Advisory


Committee of the Bharati Vidyapeeth University Medical College. Her areas of interest include High risk Obstetrics, Gynecology endoscopy, Infertility and teaching. She also holds the post of the Chairman of the Medical Disorders in Obstetrics Committee of FOGSI and is the member of the Governing Council of the Indian College of Obstetrics and gynecology. She is the editor of the National Eclampsia registry Newsletter and is the Associate coordinator of the FOGSI-ICOG National Eclampsia Registry. As the Joint Secretary, FOGSI 2010 she has contributed to the ‘Reaching the Unreached Initiative’ of FOGSI and is the Associate coordinator of the ‘Save the Mother and Newborn Initiative of FOGSI’. She also has contributed to the formulations of the Good Clinical Practice Recommendations of the FOGSI to help members in day to day practice.Prof Girija also is a scientific collaborator and principal investigator for many projects in affiliation with the Interactive Research School of Health Affairs (IRSHA), Bharati Vidyapeeth with a focused research related to micronutrients in conjunction with preeclampsia, preterm delivery, infertility and metabolic disorders. She holds many important posts at the university level such as the member of the Board of studies and the member of the antisexual harassment cell and is a postdoctoral guide. She is an invited member of the Central Supervisory Board of the PCPNDTAct of the GOI, as an advisory to the Union Health Minster. She also is the state level advisor to the government for the implementation of the NRHM for reducing maternal mortality. She is the member of the Ethics Committee of the FOGSI.Dr Girija was the only Indian invited as Speaker faculty at the IFFS meeting in Munich in 2010 and has presented her research on infections related to infertility. She also is the member of the Steering Committee of the World Organisation Gestosis an international body for preeclampsia and is the Secretary of the Indian Chapter of the Organisation Gesrtosis.A passionate teacher her postgraduate training program “IMPACT” (Imparting practical and clinical training for the Postgrduates) has been very popular in the city of Pune. Innovations in teaching and creation of standard modules for skill enhancement and assessment is her forte and has therefore received a huge acclaim for the same. She is the Executive Vice President of the Pune Obstetrics and gynecological Society and has contributed towards adolescent health care, cancer screening, anemia screening programs.A proficient speaker is invited nationally and internationally to deliberate on issues pertaining to endoscopy and high risk obstetrics to countries such a Serbia, Germany, Istanbul, Indonesia etc. Many national and international publications are to her credit has authored several chapters to well acclaimed publications.

W5-5. The effective and maintained antihypertensive management in eclampsia and HELLP syndrome by the stepwise protocol of nicardipine drip infusion with starting at low dose under referring to diastolic blood pressure.

Osamu Nakamoto1, Ikuko Mita, Sachiyo Nishimoto1, Kohji Kajitani1, Kazuharu Tanaka1, Hiroaki Nakamura1, Chika Mosohisa2

1Department of Obstetrics, Osaka City General Hospital 2Department of Obstetrics and Gynecology, Osaka City Juso Hospital

The antihypertensive therapy for the hypertensive disorders of pregnancy needs controllable and stable managements for protecting the antepartum feto-maternal circulations along with unstable postpartum circulatory conditions. Eclampsia and HELLP syndrome are the major and the most hazardous involvements in these diseases with easy to accompany with severe hypertension. Effective and maintained managements are preferable for these maternal organ involvements.Nicardipine (Nic) is the only intravenous calcium channel blockade with effective and controllable dose-response reaction. Also, we had elucidated that the elevating diastolic blood pressure (dBP) is related to the maternal organ involvements in the disease of hypertensive disorders in pregnancy. We had applied the Nic drip infusion against the disease of hypertension in pregnancy under referring to dBP. And for the safe and maintained management, Nic is started at low dose and increased in the dose in pre-ordered stepwise manner toward target dBP. We studied the change of BP in the cases of eclampisa with progressing state, and elucidated the efficacy of stepwise management with referring to dBP.We will show the effectiveness and safety the antihypertensive treatment of Nic stepwise protocol with starting at low dose and referring to dBP for the management of eclampsia along with HELLP syndrome complicating with severe thrombocytopenia below 50 × 103/mm3. And it is proposed that targeting dBP below 90 mmHg (systolic below 140 mmHg only in the isolated systolic hypertension) should be the safe way to treating eclampsia and HELLP syndrome.

Profile of Chief of department of Obstetrics, Osaka City General HospitalOsamu Nakamoto, MD, PhD

October 1959: Born in OsakaMarch 1984: Graduation from Osaka City Medical SchoolMarch 1990: Graduation from Graduate School of Medicine, Osaka City Medical SchoolOctober 1991: An Award of the two in the 7th World Congress of the International Society for the Study of Hypertension in Pregnancy. Title: Effect of the vascular endothelial cells on refractoriness to angitotensin II of pregnant and non-pregnant rabbits. Significance of EDRF (endothelium-derived relaxing factor ).December 1993: Department of Obstetrics and Gynecology, Osaka City General HospitalSeptember 1994: An Officer of the Japanese Society for the Study of Toxemia of Pregnancy (the Japanese Society for the Study of


Hypertension in Pregnancy, JSSHP from 2005)April 2008: Chief of Department of Obstetrics, Osaka City General HosptialMarch 2011: Vice-chief of the Offers of the JSSHPMarch 2013: A member of the Board of the JSSHP

W5-6. Correlation of Thrombocytopenia and LDH levels in patients with pregnancy hypertension and its comparison with normotensive pregnant women

Bhumija SharmaOBGY, Bharati Vidyapeeth Hospital and Medical College, Pune, India

Pre-eclampsia affects approximately 5–8% of pregnant women. The common hematological disorder in preeclampsia is thrombocytopenia. LDH refl ects the severity and occurrence of complications in preclampsia. Both these are useful in predicting the progression of severe preclampsia and identifi cation of HELLP syndrome . The aim of this study is to assess the levels of platelet count and serum LDH levels in patients with preclampsia and its comparison in normotensive pregnant patients so as to observe the levels which are specifi c to severity of preclampsia and infl uence decision making in obstetric intervention. It is a prospective observational study in which a total of 40 ANC patients are included, 20 of which were diagnosed to have raised blood pressure and rest of the 20 were normotensive patients at 36 weeks of gestation. Pre-eclampsia criteria were: Blood pressure more than or equal to 140/ 90 mm Hg and proteinuria greater or equal to 300 mg/ 24hours urine sample in the third trimester. Platelet, and LDH were measured. Data were analyzed by the mean of SPSS-14 program & Chi-2 or t-student were used. Both the groups were comparable in context of age and parity .10 had mild preeclampsia while 10 had severe preeclampsia. Three normotensive subjects were found to have thrombocytopenia and 15 subjects had abnormal LDH level ( > 600IU). In comparison with preeclampsia group thrombocytopenia and LDH levels are not signifi cantly different. However they are markedly abnormal in severe hypertension are infl uenced by co-existence of anemia. These laboratory parameters also infl uence obstetric decision making and are associated with fetal distress. The study concludes that thrombocytopenia and LDH levels are not specifi c parameters to diagnose the disease but are associated with fetal distress.


W6-1. Decidual cellular senescence contributes to preterm delivery.

Yasushi HirotaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Japan

Preterm delivery is a major global health issue, and its causes and underlying mechanism remain unclear. We recently established a mouse model of spontaneous preterm birth. In this model, decidual cellular senescence early in pregnancy via mTOR-p21 signaling is a major contributor of preterm delivery and fetal death, and these adverse phenotypes are restored by the inhibition of mTOR or p21. This role of decidual cellular senescence in determining the timing of birth in mouse models may help us better understand the mechanism of the timing of birth in humans and develop new and improved strategies against preterm delivery.

Biosketch:1992- Medical Student, The University of Tokyo, Japan.1998- Resident, Department of Ob/Gyn, The University of Tokyo, Japan.2001- Graduate Student, The University of Tokyo, Japan.2005- Instructor, Department of Ob/Gyn, The University of Tokyo, Japan.2006- Research Fellow, Department of Ob/Gyn, The University of Tokyo, Japan.2007- Research Fellow, Department of Pediatrics, Vanderbilt University, TN, USA.2008- Research Fellow, Cincinnati Children’s Hospital, OH, USA.2010- Chief Physician, Yaizu City Hospital, Shizuoka, Japan.2011- Research Investigator, PRESTO, Japan Science and Technology Agency, Japan.2014-present. Instructor, Department of Ob/Gyn, The University of Tokyo, Japan.


W6-2. Leukocyte activation before term and preterm labour

J Takeda1,2, B Hanson1, X Fang1, DM Olson1

1Dept Ob/Gyn & Physiology, U of Alberta 2Dept Ob/Gyn, Juntendo U, Japan

Background: The events of parturition are similar to those of an inflammatory response. Previously we demonstrated that local chemotactic activity increases as gestation progressed. However, the issue of whether leukocyte responsiveness changes during pregnancy was not addressed. We hypothesized that leukocyte responsiveness to a chemotactic signal increases as gestation progresses.Methods: Proteins were isolated from fetal membranes. Blood was drawn from 5 different groups of patients; term in labour (TL), term not in labour (TNL), preterm in labour (PTL), threatened preterm labor (TPTL), fluid leakage (pPROM) and preterm not in labor (PTNL). Isolated leukocytes and chemotactic extracts were placed into a Boyden chamber. Migrated leukocytes were quantitated using flowcytometry. The expressions of 5 chemokine receptor mRNA abundance in leukocytes were assessed using quantitative RT-PCR.Results: Leukocyte responsiveness increased to term chemotactic signals as labor progressed (p < 0.0001). Subanalysis revealed spontaneous TL leukocytes migrated more than induced labor leukocytes (p < 0.05). PTL and pPROM leukocytes migrated more than PTNL and TPTL leukocytes (p < 0.05). However, chemokine receptors expression did not change in any group.Conclusions: This is the first report that human leukocytes increase their responsiveness to chemotactic signals as labor progresses. This approach can be used to establish a preterm labor prediction test. The lack of change in leukocyte chemokine receptor expression suggests the intriguing possibility of a different type of chemoattractant.

CURRICULUM VITAEEducation4/1/2002 -3/31/2008 Juntendo University, Tokyo. Awarded the degree of M.D.

Research and professional experience:4/1/2008 -3/31/2010 Junior Resident in Saitama medical center, Saitama.4/1/2010 -9/30/2010 Senior resident at the Dept. of OB & GYN in Juntendo University Shizuoka Hospital, Tokyo10/1/2010 -6/30/2011 Senior resident at the Dept. of OB & GYN in Juntendo University Hospital, Tokyo4/7/2011 -4/10/2011 Volunteer at Kesennuma City Hospital, The 2011 off the Pacific coast of Tohoku Earthquake7/1/2011 -7/31/2011 Senior resident at Okinawa Yaeyama Hospital, Okinawa8/1/2011 -3/31/2012 Senior resident at the Dept. of OB & GYN in Juntendo University Urayasu Hospital, Chiba4/1/2012 -present Juntendo University Graduate school of medicine9/2/2012 -present Post-doctoral fellow at University of Alberta

W6-3. Trial for prevention of preterm birth in Japan

Katsufumi OtsukiChief and Associate Professor, Department of Obstetrics and Gynecology, Showa University Koto Toyosu Hospital

The perinatal mortality rate in Japan is the lowest in the world, but the mortality rate is high for preterm infants born at less than 30 weeks gestation. Moreover, even if they survive, preterm infants face a wide variety of problems. To improve prognosis for these infants, focus must be placed not only on improvements in neonatal care, but also on reducing preterm deliveries themselves. Based on recent research, new markers and methods for testing for threatened preterm delivery are being clinically introduced, but we are currently still at the stage of exploring how such new test methods and knowledge can be utilized in actual clinical practice to prevent preterm deliveries. Clinical research is rapidly advancing in this area. As we cannot just rely on the results of foreign research in this field, research that has been adapted to the specific conditions of perinatal care in Japan is crucial. However, due to the small scale of medical facilities in Japan, we have yet to see reports of good clinical research using the principles of evidence-based medicine. Thus, for the present study, we organized a group composed mainly of university hospitals and general perinatal care centers in Japan and conducted a full-scale randomized comparative clinical trial with the objective of preventing preterm deliveries, the most important topic in perinatal care. Therefore, the objective of our multicenter, randomized, controlled trial was to assess the benefits of some treatments on women with ultrasound-diagnosed cervical shortening in the mid-trimester to prevent preterm birth.

EDUCATIONAL HISTORY1991 M.D. Showa University, School of Medicine1997 Ph. D. (Dr. of Medical Science) Showa University, School of Medicine

PROFESSIONAL BACKGROUND (EMPLOYMENT HISTORY)May/1991 passed the Examination of National BoardMay/1991-


Resident in Showa University HospitalJan/1992- Medical Staff, Department of Obstetrics and Gynecology, Haibara General HospitalMay/1993- Medical Staff, Department of Obstetrics and Gynecology, Kameda General HospitalMay/1994- Medical Staff, Department of Obstetrics and Gynecology, Showa University HospitalJan/1997- Medical Staff, Department of Obstetrics and Gynecology, Ohguchi-Higashi General HospitalMay/1998- Medical Staff, Department of Obstetrics and Gynecology, Showa University HospitalJun/1999- Visiting Scholar at University of California Davis (CA, U.S.A.) Mentor 1: Professor Bo L. Lonnerdal University of California Davis, Department of Nutrition, Mentor 2: Professor Michael P Sherman University of California Davis, Department of Pediatrics, Division of NeonatologyJun/2001- Medical Staff, Department of Obstetrics and Gynecology, Showa University HospitalApr/2003- Chief of Maternal-Fetal-Intensive care-Unit, Department of Obstetrics and Gynecology, Showa University HospitalOct/2005- Asssistant Professor, Department of Obstetrics and Gynecology, Showa University HospitalJune/2013- Associate Professor, Department of Obstetrics and Gynecology, Showa University Northern Yokohama HospitalMarch/2014- Chief and Associate Professor, Department of Obstetrics and Gynecology, Showa University Koto Toyosu Hospital

W6-4. The effect of appropriate antibiotic therapy to preterm labor with intraamniotic infection

Satoshi Yoneda, Noriko Yoneda, Mika Ito, Arihiro Shiozaki, Shigeru SaitoDepartment of Obstetrics & Gynecology, University of Toyama, Toyama-Shi, Toyama 930-0194. Japan

Objective:To examine whether antibiotic therapy is useful to prevent preterm birth.Study design:Ninety-one preterm labors with intact membrane less than 32 weeks of gestation were enrolled. They were all managed in our hospital and obtained informed consent for amniocentesis. Amniotic fluid microbes were detected by newly established - high sensitivity PCR method. Cephalosporin iv infusion were performed in bacteria only cases, and antibiotic macrolide therapy was performed to Ureaplasma / Mycoplasma only cases, or the both therapies were performed to coinfection cases. We evaluated the correlations between the prolonged gestational days and the appropriate antibiotic therapy (AAT), including the cerclage, 17-OHPC, and urine trypsin inhibitor (UTI).Results:AAT was the independent factor to influence the prolonged gestational days in regression analysis (P = 0.0002). In the negative microbe group (n = 58), the prolonged gestational days in the administration of antibiotics were significantly shorter than that of no administration (P = 0.0109). While in the positive group (n = 33), AAT tended to prolong the gestational days, compared with no AAT (P = 0.0734). The frequency of neonatal sepsis, and chronic lung disease did not increase in AAT group.Conclusion:The appropriate antibiotic therapy may be a useful therapy for prolongation of gestational days in preterm labor.

Satoshi YonedaAssistant ProfessorDept. of Obstetrics and Gynecology, University of Toyama, JapanToyama University M.D. 1996 MedicineToyama University Ph.D. 2008 Medicine


Professional Positions:1998-1999 Aiiku hospital (Tokyo)2000-2001 Kagoshima city hospital (Kagoshima)2001- Assistant Professor, Toyama University

Awards and Other Professional Activities2009 YOUNG SCIENTIST AWARD, The 21st AOCOG (Asian & Oceanic Congress of Obstetrics & Gynecology)2012 Perinatal Obstetrician2013 Yuji Murata AWARD, The 23rd AOCOG (Asian & Oceanic Congress of Obstetrics & Gynecology)

W6-5. Antenatal corticosteroids; Anything new after Liggins?

Alex C. Vidaeff

Baylor College of Medicine, Houston, USA

The administration of antenatal corticosteroids is one of the most effective and important therapies in prenatal medicine. Clearly, antenatal corticosteroids have very substantial immediate benefits for preterm infants with few known side effects.Several aspects are still the subject of ongoing controversy and uncertainty such as the ideal drug formulation, timing of treatment, or the applicability to specific clinical conditions. Growth restricted fetuses contribute to a subset of preterm infants that may be particularly vulnerable to corticosteroid therapy and the potential adverse effects of corticosteroids in this clinical context continue to be debated. Our presentation will point out questions that still need answers and represent current priority areas for future research intended to devise ways in which the effectiveness and safety of antenatal corticosteroids can be enhanced.

BIOGRAPHICAL SKETCHNAMEVidaeff, Alex C.

POSITION TITLEProfessor of Obstetrics & GynecologyBaylor College of MedicineBIRTHDATE

11,04,1951EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, and include postdoctoral training.)

INSTITUTION AND LOCATION DEGREE(if applicable) YEAR (s) FIELD OF STUDY

Faculty of General Medicine, Bucharest, Romania M.D. 1977 MedicineBucharest Hospitals, Romania 1976-1979 Internship-Surgical specialtiesFilantropia Hospital, Bucharest, Romania 1980-1981 Residency – Ob/GynLenox Hill Hospital, New York, New York 1986-1987 Residency – PathologyMount Sinai Hospital, Chicago, Illinois 1987-1989 Residency-Ob/Gyn (PGY 1-2)Temple University, Philadelphia, Pennsylvania 1989-1991 Residency-Ob/Gyn (PGY 3-4)University of Texas Medical School, Houston, Texas 2000-2003 Fellowship-Maternal-Fetal MedicineUniversity of Texas School of Public Health, Houston, Texas M.P.H. 2001-2003 Master of Public Health

A. Positions and Honors.Positions and Employment1986-1987 Medical Residency, Department of Pathology, Lenox Hill Hospital, New York, New York1987-1989 Medical Residency, Department of Obstetrics and Gynecology, Mount Sinai Hospital, Chicago, Illinois1989-1991 Medical Residency, Department of Obstetrics and Gynecology, Temple University, Philadelphia, Pennsylvania1991-1999 Clinical Instructor, Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA1999-2001 Assistant Clinical Professor, Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School,

Boston, MA2000-2003 Medical Fellow, Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences,

University of Texas Health Science Center at Houston, Houston, Texas2003-2009 Associate Professor, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Texas Health Science

Center at Houston, Houston, Texas2006-2011 Associate Faculty Member, Graduate School of Biomedical Sciences, University of Texas-Houston2007-2011 Associate Professor, Department of Gynecologic Oncology, MD Anderson Cancer Center, Houston2009-2011 Professor, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Texas Health Science Center at

Houston, Houston, Texas2006-2011 Director, Research, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Texas Health Science

Center at Houston, Houston, Texas


2011- Professor, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas2012- Professor, Department of Gynecologic Oncology, MD Anderson Cancer Center, HoustonHonors1976 First National Romanian Prize for Medical Research – Medical Students1977 Diploma for Distinguished Professional Merits of the University of Bucharest1996 Honorary Member of the Romanian Society of Obstetrics and Gynecology1999 Honorary Member of the Romanian Society of Assisted Human Reproduction2003 Obstetrics /Pediatrics Society for Maternal-Fetal Medicine 43rd Annual Meeting Scholarship Award for Fellows2003-2010 Member Steering Committee, International Society for the Study of Pathophysiology of Pregnancy –Organization Gestosis2006 Senior Member, American Institute of Ultrasound in Medicine2010- Chairman Steering Committee, International Society for the Study of Pathophysiology of Pregnancy2011 Dean’s Teaching Excellence Award, University of Texas Houston Medical School


W7-1. Epidemiology of preeclampsia in Japan

Arihiro Shiozaki1, Yoshio Matsuda2, Shoji Satoh3, Shigeru Saito1 1Department of Obstetrics and Gynecology, University of Toyama, Toyama, Japan

2Department of Obstetrics and Gynecology, International University of Health and Welfare, Tochigi, Japan3Maternal and Perinatal Care Center, Oita Prefectural Hospital, Oita, Japan

Currently, preeclampsia (PE) and gestational hypertension (GH) are considered either separate diseases affecting similar organs or different severities of the same underlying disorder. Using data from women with no essential hypertension and with singleton births between 2001 and 2005 after 22 weeks of gestation at 125 centers in Japan (Japan Perinatal Registry Network Hospitals), we focused on the difference in risk factors and in perinatal outcomes between GH and PE. Of 241,292 women, 2,808 (1.2%) developed GH and 6,423 (2.7%) developed PE. Thirty-fi ve years or older, primiparity, diabetes mellitus, and renal disease increased the risk of both GH and PE. Forty years or older was a factor only for GH, while primiparity, female fetus, and renal disease were risk factors only for PE. Early-onset (before 32 weeks of gestation) was a common risk small-for-gestational age (SGA) in GH and PE, but in late-onset only PE was a risk factor for SGA. Main population of SGA infants was composed of PE cases because PE accounted for 83.3% of early-onset type before 32 weeks. Girl preponderance in the PE women was observed (sex ratio: boys/girls = 0.904), while slight boy preponderance was seen in normotensive women (1.06) and GH (1.02). These fi ndings suggest that PE and GH seem to be independent entities.

CVArihiro Shiozaki, MD, PhD, Associate Professor, Department of Obstetrics & Gynecology, Toyama University Hospital, Toyama, Japan1986/04 Toyama Medical and Pharmaceutical University1987/04 Toyama Red Cross Hospital, Toyama1988/01 Iiyama Red Cross Hospital, Nagano1989/04 Toyama Medical & Pharmaceutical University, Toyama1990/04 Saiseikai Takaoka Hospital, Toyama1990/06 Toyama Medical & Pharmaceutical University, Toyama1992/04-94/04 Michigan State University, Research Associate, U.S.A.1994/04 Toyama Medical & Pharmaceutical University, Toyama1994/07 Kanagawa Children’s Medical Center, Kanagawa1995/03 Toyama Medical & Pharmaceutical University, Toyama1996/04 Itoigawa Sogo Hospital, Niigata1998/04 Shakaihoken Takaoka Hospital, Toyama2002/04 Tonami General Hospital, Toyama 2002/09 Toyama Medical & Pharmaceutical University, Toyama2005/04 University of Toyama, Toyama


W7-2. Outcome of pregnancy with isolated proteinuria - gestational proteinuria can detect the onset of preeclampsia

Mamoru MorikawaDepartment of Obstetrics, Hokkaido University Graduate School of Medicine

In 2005, the Japanese Society of Obstetrics and Gynecology revised the criteria for pregnancy-induced hypertension and adopted new criteria in which PIH was defined as hypertension with or without proteinuria occurring at and after 20 weeks of gestation, but resolving 12 weeks postpartum. PIH includes preeclampsia (hypertension with proteinuria), gestational hypertension (hypertension without proteinuria) and superimposed preeclampsia. Women with proteinuria alone are not diagnosed with preeclampsia until they exhibit additional hypertension, and those who do not develop hypertension are diagnosed as having gestational proteinuria at 12 weeks postpartum. Thus, gestational proteinuria is a retrospective diagnosis.I. Problems in methods for the detection of significant proteinuria in pregnancy and for the diagnosis of gestational proteinuria.Dipstick test and P-test were likely to over- and underestimate risks of significantproteinuria, respectively. Thus, the spot-urine protein-to-creatinine ratio (P/Cr test) would be used. The 24-h urine collection was often incomplete. Repeated positive dipstick test results in two successive antenatal visits warrant a need for a confirmation test of significant proteinuria.II. Gestational proteinuria can detect the onset of preeclampsiaWomen with new-onset proteinuria in the absence of hypertension may be more likely to progress to preeclampsia than women with a presumptive diagnosis of gestational hypertension, and the likelihood of progression may be significantly greater among women with earlier presentation.

Curriculum VitaePERSONAL DATA

Name: Mamoru MorikawaDegree: M.D. Ph.D.Institution: Hokkaido University Graduate School of Medicine, Department of ObstetricsDate of Birth: 20 June 1968

EDUCATION (Graduation)1994 Asahikawa Medical University Graduate School of Medicine (MD)2002 Hokkaido University Graduate School of Medicine (PhD)

WORK EXPERIENCE1994 – present: Hokkaido University Graduate School of Medicine, Department of Obstetrics and Gynecology2007 – 2012: Assistant Professor, Department of Obstetrics2012 – present: Physician-in-Chief, Perinatal Medical Center2013 – present: Lecturer, Department of Obstetrics

STUDY ABROAD2007 Service de Gynecologie Obstetrique, CHI de Poissy Saint-Germain-en-Laye, France (Université de Versailles-St-Quentin en Yvelines) Professor Yves VILLE

AWARD2009 The Japan Society of Obstetrical, Gynecological & Neonatal Hematology. Best presentation award2012 The Hokkaido Obstetrical and Gynecological Society. Best Paper Award2013 The Japanese Society of Diabetes and Pregnancy. Best presentation award

SPECIAL FIELDPreeclampsia, obstetric hemorrhage, coagulation disorder, multiple pregnancy, fetal therapy

W7-3. Standard range of home blood pressure during pregnancy

Akinori Miki1, Kazuko Sato1, Atsuo Itakura2, Yoshimasa Kamei1, Osamu Ishihara1

1Department of Obstetrics and Gynecology, Saitama Medical University 2Department of Obstetrics and Gynecology, Juntendo University

IntroductionHome Blood Pressure (HBP) measurement is widely spread to manage hypertensive disorder worldwide but, in obstetric field, HBP measurement is still not a standard method to manage pregnant induced hypertension (PIH). We collected the HBP in pregnant women and assessed the trend of HBP during pregnancy.Patients and MethodsFive hundred seventy one pregnant women were recruited to this study. The electric sphygmomanometer for home use was provided


before 15 weeks of pregnancy. The HBP measurement was recommended to perform just after getting up and before sleep, three times in each measurement.The onset of PIH was observed in 51 women and data from these women were omitted. The HBP date from 520 women were analyzed.ResultsThe HBP in 10 weeks of pregnancy was 103.0 ± 10.1 / 61.3 ± 8.7mmHg (systolic pressure / diastolic pressure). The HBP in 20, 30, and 40 weeks of pregnancy was 103.6 ± 9.9 / 59.4 ± 8.4mmHg, 105.3 ± 10.5 / 60.7 ± 8.8mmHg, and 112.4 ± 10.5 / 66.8 ± 8.6mmHg (systolic pressure / diastolic pressure) respectively. The home systolic pressure rose up during pregnancy and decline of systolic pressure in the second trimester was not observed. The home diastolic pressure was observed to hit the bottom in 20 weeks of pregnancy and continue to rise up after the bottom. The pulse rate was maximized in the 32 weeks of pregnancy and decreased until delivery.No difference was observed in the home systolic pressure between getting up and before sleep. Otherwise, the home diastolic pressure was observed to 5 mmHg higher just after getting up than before sleep.DiscussionThe trend of pulse rate is considered to relate to the circulating plasma volume in pregnant women which is also maximized in the 32 weeks of pregnancy. The drop of blood pressure in the second trimester is observed only in home diastolic pressure. Through this result, the trend of home blood pressure during pregnancy might be different from the trend of office blood pressure.

Curriculum VitaeBorn on 6th. March. 1968, in Tokushima, Japan.Entered the elementary school in Tokushima City, Tokushima Prefecture, in 1974.Entered the junior high school in Tokushima City, Tokushima Prefecture, in 1980.Entered the senior high school in Tokushima City, Tokushima Prefecture, in 1983.Admitted to the University of Tokyo, junior course in April 1986.Won a scholarship from the Tokushima Newspaper Company for 6 years.Admitted to the medical school, Faculty of Medicine in April 1988.Graduated from the medical school in March 1992.Started internship at the University of Tokyo Hospital, Department of Obstetrics and Gynecology in April 1992.Got training as an anesthetist at the Tokyo Police Hospital from December 1992 to March 1993.Admitted to the Hitachi General Hospital, Hitachi Ltd., in September 1993.Admitted to the graduate school, Faculty of Medicine, University of Tokyo in April 1995.Started investigation about the reproductive immunology.Transferred to Central Blood Center, Japan Red Cross in July 1995.Transferred to the University of Tokyo Hospital in February 1998.Graduated from the graduate school in March 1999.Admitted as a research assistant to the Saitama Medical Center, Saitama Medical School in April 1999.Admitted as a research assistant to the University of Tokyo Hospital in September 2000.Admitted as a postdoctal research fellow to the Fred Hutchinson Cancer Research Center (Seattle, WA, USA) in December 2001.Admitted as a postdoctal fellowship for research abroad by Japan Society for the Promotion of Science (JSPS) in April 2002.Continued as a postdoctal research fellow to the Fred Hutchinson Cancer Research Center (Seattle, WA, USA) until March 2004Admitted as an assistant professor to the Saitama medical University in April 2004

W7-4. Out-of-office blood pressure monitoring during pregnancy

Hirohito Metoki1,2, Takayoshi Ohkubo3, Noriyuki Iwama2, Mami Ishikuro1,2, Taku Obara1,2, Hidekazu Nishigori2, Takashi Sugiyama2, Junichi Sugawara1,2, Shinichi Kuriyama1,2,

Kazuhiko Hoshi4, Masakuni Suzuki4, Nobuo Yaegashi1,2, Yutaka Imai21Tohoku Medical Megabank Organization, Tohoku University

2Tohoku University Graduate School of Medicine and Pharmaceutical Sciences 3Teikyo University School of Medicine

4Suzuki Memorial Hospital

Blood pressure measurement is the most important issue for diagnosis of hypertension. For hypertensive disorders during pregnancy, the measurement is also important. Blood pressure measurement is classified into conventional clinic blood pressure measurement and out-of-office blood pressure measurements. Out-of-office blood pressure measurements consists of ambulatory blood pressure measurement and home blood pressure measurement. They are strongly recommended for using for diagnosis and treatment of hypertension. Recent Guideline of Japanese Society of Hypertension recommended using home blood pressure measurement when home blood pressure and clinic blood pressure indicate different diagnosis criteria. Although this recommendation for hypertension is based on the several evidence from not only cross-sectional study, but also longitudinal observation study which observed long-time prognosis, there are little evidence of out-of-office blood pressure measurement for pregnant women.We have studied home and clinic blood pressure change during pregnancy among women who consented to measure their home blood pressure from early pregnancy to 1-month after delivery (the Babies and their parents’ longitudinal Observation in Suzuki memorial Hospital on Intrauterine period (BOSHI) study). In this workshop, some results from the BOSHI study will be presented.


Curriculum VitaeContact Details: Name Hirohito Metoki Office Address Department of Community Medical Supports, Tohoku Medical Megabank Organization, Tohoku University 2-1 Seiryo-cho, Aoba-ku, Sendai, 980-8573, Japan Telephone + 22-717-8104 Email [email protected] degrees: M.D. Tohoku University School of Medicine in 2001 Ph.D. Tohoku University Graduate School of Medicine in 2007Professional Experiences: Resident of internal medicine at Osaki citizen hospital, From May 2001 to September 2003 From April 2004 to September 2004 Research Fellow of the Japan Society for the Promotion of Science, Department of Medical Genetics, Tohoku University Graduate School of Medicine From April 2007 to March 2010 Assistant Professor, Department of Obstetrics and Gynecology, Environment and Genome Research Center, Tohoku University Graduate School of Medicine From April 2010 to March 2012 Lecturer, Department of Community Medical Supports, Tohoku Medical Megabank Organization, Tohoku University From April 2012

W7-5. Prediction of preeclampsia using angiogenesis-related factors or home blood pressure monitoring

Akihide Ohkuchi1, Chikako Hirashima1, Miyuki Saruyama1, Kayo Takahashi1, Takako Ohmaru2, Hirotada Suzuki1, Shigeki Matsubara1, Mitsuaki Suzuki1

1Obstetrics and Gynecology, Jichi Medical University School of Medicine, Tochigi 2Obstetrics and Gynecology, Kyushu University, Fukuoka, Japan

Aim: To evaluate the screening performance of plasma level of soluble fms-like tyrosine kinase 1 (sFlt-1) /placental growth factor (PlGF) ratio or home blood pressure monitoring (HBPM) for predicting the occurrence of preeclampsia (PE).Methods: In the first study, using sFlt-1/PlGF ratio during 19-31 weeks determined by an automated electrochemiluminescence immunoassay, we developed prediction of imminent onset of PE with onset at < 4 weeks after blood sampling. In the second study, using the weeks at inflection point in HBPM, we developed prediction of PE.Results: In the first study, the onset threshold of the sFlt-1/PlGF ratio was determined using 25 women with PE. The imminent onset of PE was identified in 0.2% (2/1199) at 19–25 weeks and in 0.8% (6/798) at 26–31 weeks. The onset threshold of the sFlt-1/PlGF ratio at 19–25 weeks yielded sensitivity (SE) of 100% and specificity (SP) of 100%; the onset threshold of the sFlt-1/PlGF ratio at 26–31 weeks yielded SE of 83% and SP of 99.4%. In the second study, the inflection point was observed in 80% (12/15) of PE, and it occurred median 4 weeks before the onset. Using 30 normal pregnant women and 15 women with PE, the cutoff level of 30 weeks of the inflection point yielded SE of 53% and SP of 93%.Conclusion: The detection of the level of sFlt-1/PlGF ratio at 19-31 weeks or HBPM during the latter half of pregnancy period may be clinically useful for predicting the occurrence of PE.

Name: Akihide OhkuchiDate of Birth: 12 Dec 1962Education:

1981–1987: Jichi Medical University School of Medicine, Tochigi, Japan. Major: Medicine1987: License for medical doctor1998: License for a specialist for Obstetrics and Gynecology2001: PhD from Jichi Medical University2009: License for a specialist for Perinatology (Maternal Fetal Medicine)

Work Experience:1987–1989: Toyama Prefectural Central Hospital, Toyama, Japan.1998–: Department of Obstetrics and Gynecology, Jichi Medical University School of Medicine, Tochigi, Japan2002–2007: Lecturer


2007–: Associate Professor.Specialty:

Perinatal medicine; Preeclampsia; Clinical Research SupportSocial role:

2006–: Associate editor in the Journal of Obstetrics and Gynecology2011–: Editor in the Case Report in Obstetrics and Gynecology2013–: Editor in the Medical Journal of Obstetrics and Gynecology2013–: Editor in the Jichi Medical University Journal

Awards:2010 The Most Valuable Paper Award -2010 Jichi Medical University2012 The Most Valuable Paper Award -2012 Jichi Medical University2012 Roche Diagnostics Best Poster Award


W8-1. The occiput spine angle: a new sonographic index of fetal head defl exion during the fi rst stage of labor

Tullio GhiObstetrics and Gynaecology, S. Orsola Malpighi Hospital, Bologna, Italy

1) objectives: To assess sonographically the degree of fetal head defl exion during the 1st of labor and to evaluate the reproducibility of this parameter.2) methods: In a non consecutive series of women during the 1st stage of labor with the fetus in occiput anterior position, the angle between the occipital bone and the cervical spine of the fetus (occiput-spine angle or OSA) was measured by 2D ultrasound by operator A (Fig 1). The sonographic picture was stored in the archive of the machine and the measurement was repeated at distance by the same examiner and by a different one (operator B). The intra- and interobserver reproducibility of this measurement was assessed by means of intraclass correlation coeffi cient.3) results: Overall 33 women in the fi rst stage of labor were included in the study group. The OSA was measured at a mean cervical dilatation of 4.0 ± 0.9 cm and showed a mean value of 128.7 ± 12.5°. OSA measurements showed excellent intra- and interobserver agreement (intraobserver 0.87, 95% CI 0.75-0.93; interobserver 0.82, 95% CI 0.67-0.91).4) conclusions: In fetuses with occiput anterior position, the degree of fetal head defl exion during the 1st of labor may be reliably measured by transabdominal 2D ultrasound. A larger population is required in order to investigate if this new sonographic parameter has a correlation with labor outcome.

W8-2. The effectiveness of ultrasound examination to detect the antenatal viral infection in normal and preeclampsia complicated pregnancy

Alexander PapitashviliProfessor of Tbilisi Medical College VITA, Senior Specialist on Medical Ultrasound of Tbilisi Medical Center NEOCLINICA,

GEORGIA

ObjectivePreeclampsia is a common pregnancy disorder that originates in the placenta and causes variable maternal and fetal problems. In the worst cases, it may threaten the survival of both mother and baby.There are different models for the pathogenesis of preeclampsia and the infl ammatory model is one of them because of growing body of evidence suggested for a causal link between maternal infection and preeclampsia. Maternal infection, including viral infection, are very important in the pathogenesis of preeclampsia.Also the intrauterine infection are one of the most frequent causes of perinatal mortality may account for as much as 20% of fetal and neonatal disease. A lot of pregnancies are complicated by clinically overt viral infectious illnesses and many more may be affected by silent viral infection.Any infection (bacterial or viral) is associated with a two fold higher risk of preeclampsia. The double impact of infection both to maternal and foetal status on both sides, directly and next indirectly - intensifying the grave alterations adding the preeclampsia, cause the different complications with increasing risk of maternal & foetal morbidity and mortality.


Preeclampsia/eclampsia is really one of these expected complications that needs as key aspect the efficient prenatal care for monitoring pregnancies. Ultrasonography is one of main diagnostic tools needed for prenatal care.The aim of study was to evaluate how useful is the ultrasound examination to detect the alterations specifically for the antenatal viral infection in normal and preeclampsia complicated pregnancy, also to predict the manifestation of preeclampsia in pregnant affected by intrauterine viral infection.Methods1. Screening ultrasound examination (USD) were performed in 2,577 clinically healthy pregnant in 2nd and 3rd trimester - group 12. Ultrasound examination were performed in untreated 78 pregnant in 2nd and 3rd trimester with intrauterine viral infection(IVI)

primary identified by biochemical markers - group 23. Ultrasound examination were performed in 35 pregnant in 2nd and 3rd trimester with clinically overt symptoms of preeclampsia - group 3Cross-correlation analysis was performed in these three groups and used special statistical methods.Results

Screening USD ( 2,577 pregnant- group 1 )specific changes in the fetus and placentadetermined in 37 pregnant (1.44 %)none determined in 2,540 pregnant (98.56%)persistence of infectiondetected 23 (62.0 % of 37 pregnant)none detected 14 (38.0 % of 37 pregnant)

Persistence of viral infection (78 pregnant with primary biochemically identified IVI - group 2)specific changes in the fetus and placentadetermined in 28 cases (35.8 %)none detemined in 50 cases (64.2 %)

Preeclampsia (35 pregnant - group 3)specific changes in the fetus and placentadetermined in 31 cases (88.6 %)none detemined in 4 cases (11.4 %)

ConclusionUltrasound scanning is capable to detect most of the grave alteration typical of fetal infection.Doppler studies can be used to study alterations in vascular flow that result from congenital infection.Ultrasound scanning is capable to predict the manifestation of preeclampsia in pregnant affected by intrauterine viral infection.The use of the routine ultrasound examination as a separate screening test to detect viral intrauterine infection has certain limitations and further biochemical tests are desirable.

CURRICULUMPAPITASHVILI Alexander, b. October 20,1949, Orjonikidze (former USSR)Medical DoctorEducation:

Graduate, Tbilisi State Medical University, Georgia, 1972PhD, Moscow Central Research-Scientific Institute of Obstetrics&Gynecology of USSR Health Care Ministry, 1976;Associate Professor, Tbilisi State Medical University, 1990;Professor, Tbilisi Medical College VITA, 1994;

Appointment:Associate Professor, Tbilisi State Medical University, 1990;Professor, Tbilisi Medical College VITA, 1994;

Publication:157 scientific publication in the field of human reproduction and genetics, obstetrics and gynecology, prenatal and perinatal medicine, ultrasound in medicine, medical demography, mathematical modeling and expert systems in medicine.Inventor of State Certified method of sonohysterosalpingography, owner of Copyright Certificate, 1983. The named method has been offered by the author in clinical practice in since 1979 for the first time in the world.Grounder and pioneer of Ultrasound Examination in Obstetrics and Gynecology in the former USSR and Georgia.

Honour:Winner, Ukrainian Davidenkov Medical Prize, 1997;Listed in the 2003/2004 edition of Contemporary WHO’S WHO issued by American Biographical Institute;Listed and signed in 2004 by International Biographical Centre, Cambridge, Englandamong 2,000 OUTSTANDING INTELLECTUALS OF THE 21TH CENTURY.

Memberships:President, Georgian Association of Scientists and Specialists, Department of Medicine;President, Georgian Fetal Medicine FoundationSecretary General, Georgian Association of Prenatal Medicine and Perinatology;Director, Georgian Branch of Ian Donald International Interuniversity School of Ultrasound in Obsterics and GynecologyBoard Member, World Association of Perinatal Medicine,Representative of Ukrainian Association of Ultrasound in Obstetrics&Gynecology and Genetics in Georgia;General Member, American Institute of Ultrasound in Medicine,;Founder, Georgian branch of Fetal Medicine Foundation(FMF)Founder, Organizer and Coordinator of fifty (50) Annual and International Meetings on Medicine in Georgia between 1997-2013;


Participant and speaker more than 100 World, European and International Congresses.Member of Advisory Board of 10 Scientific Journal on Medicine.

Address: 16a, Irakli Abashidze str, Tbilisi 0179, GEORGIAphone: + 995 99 554351fax: + 995 32 223669E-mail: [email protected]

W8-3. Uterine artery Doppler longitudinal changes and early-onset intrauterine growth restriction: a case-control study

Alessandra CurtiDepartment of Medicine and Surgery DIMEC–Division of Prenatal Medicine,

St. Orsola Malpighi Hospital, University of Bologna, Bologna, Italy

Objective: To evaluate the longitudinal changes in uterine artery Doppler pulsatility index (UtAPI) in pregnancies complicated by early-onset intrauterine growth restriction (IUGR).Method: This was a retrospective case–control study including 53 singleton pregnancies affected by IUGR at 20-28 weeks and confirmed at delivery (cases), matched for gestational age with 1000 controls. Measurement of UtAPI was taken every 4 weeks between 20 and 34 weeks of gestation. Multivariable analyses were used to estimate the UtAPI as a function of both gestational age and IUGR severity. Finally, bootstrapping technique was used to internally validate our models.Results: Regression line for IUGR cases having Log10 UtAPI as dependent variable was a function of both gestational age and IUGR. Also a significant interaction between the two predictors was found, showing a divergent pattern throughout pregnancy between cases and controls. In fact, at 20 weeks the UtAPI ratio between cases and controls was 1.84, but at 30 weeks it raised to 2.05. Finally, the birth weight was inversely correlated with the UtAPI values.Conclusion: We presented a reliable multivariable statistical model to evaluate the longitudinal changes of UtAPI values as a function of both gestational age and IUGR.

W8-4. First trimester prediction of ischemic placental disease

Michael Sindos

Consultant Obstetrician-Gynaecologist Fetal maternal medicine unit and High risk pregnancy ward, 1st Department of Obstetrics and Gynaecology,

Alexandra Maternity Hospital, University of Athens, Greece

Ischemic placental disease (IPD) is a relatively new term that describes the poor placentation and vascular insufficiency of the placental unit in early pregnancy. IPD is characterized by various clinical manifestations of preeclampsia, intrauterine fetal growth restriction, and placental abruption. It seems that these three clinical conditions share a common underlying pathophysiology. That makes IPD the leading cause of iatrogenic preterm delivery ranging from the periviable to late preterm period. Increased risk of poor maternal and neonatal outcomes makes early prediction and prevention of IPD very important. Various serum and ultrasound markers have been used for the prediction and prevention of IPD during the second and third trimester of pregnancy. However it seems that prediction of IPD during the first trimester of pregnancy is of greater importance as it may help to the development of more effective prevention strategies. The current models for the prediction of IPD use a combination of maternal history and characteristics, mean maternal arterial blood pressure, maternal serum Pregnancy- Associated Plasma Protein-A (PAPP-A), mean maternal uterine arteries Pulsatility Index (UtA PI) and Placental Growth Factor (PIGF). These models provide low false positive rates ranging from 5 to 10%, and relatively high predictive rates of severe preeclampsia (95%) and Small for Gestational Age (SGA) fetuses prior to 34 weeks of gestation (55%). Administration of low dose aspirin or Low Molecular Weight Heparin, in early pregnancy, to those pregnant women identified as high risk, may be helpful in the prevention of IPD. Further larger scale studies are necessary.

Michael Sindos, MD, PhD.,Consultant Obstetrician-GynaecologistFetal maternal medicine unit and High risk pregnancy ward,


1st department of Obstetrics and Gynaecology,Alexandra Maternity Hospital, University of Athens, Greece.

He studied medicine (ΜD degree 1990) at the University of Athens. He was trained as an Obstetrician Gynecologist in the 1st Department of Obstetrics and Gynecology of the University of Athens and in the United Kingdom (The Whittington Hospital, University College London, UK). He has worked with Professor David Latchman for 26 months doing basic research in the Medical Molecular Biology Unit, Institute of Child Health, UCL, London, U.K.He has been working since 2007 as a consultant obstetrician-gynaecologist in the Fetal maternal medicine Unit and High risk pregnancy Ward, of the 1st department of Obstetrics and Gynaecology, at Alexandra Maternity Hospital, University of Athens, Greece.He is the author and co-author of 36 papers in International peer-reviewed journals and has written 1 chapter in an International and 3 chapters in Greek medical books.


W9-1. Preeclampsia complicated by other medical disorders

Sanjay GupteGupte Hospital & Centre for Research in Reproduction, Pune, India

Hypertension in pregnancy can be because of preeclampsia or it can also be due to chronic disease leading to hypertension. Such disorders can be vascular, endocrine, renal or of connective tissue origin. When these disorders are present; patient may often get superimposed. When this happens the pregnancy outcome defi nitely worsens. Hence it is important to diagnose these conditions early. Preferably diagnosis should be made preconceptionally & the management should start there & then. The preconceotional counseling & modifi cations of medication after proper assessment are vitally important for such patients & can make a difference in saving lives. Further on during pregnancy multidisciplinary approach is required to achieve reasonably acceptable outcome of pregnancy. Here we would like to present our experience with such cases of chronic hypertensive diseases which were further complicated with preeclampsia.

DR. SANJAY A. GUPTEDirector - Gupte Hospital of Accurate Diagnostic (P) Ltd.Trustee - Asmita Medical Foundation Trust

Professional Qualifi cations:-♦ D.G.O. December 1976 - 1st in Pune University.♦ M. D. (Gynecology and Obstetrics) December 1977- 1st in Pune University.♦ F. I.C.O.G. Fellow of the Indian College of Obstetrics and Gynecology 1998.♦ L.L.B. (Bachelor of Law) in 1994 with Distinction.♦ F.R.C.O.G. (Honoris causa) by the RCOG (London) November2010.

Professional Achievements:-♦ President FOGSI (2010) Federation of Obstetrics & Gynecological Societies of India.♦ President DIPSI 2013 (DIABETES IN PREGNANCY STUDY GROUP - INDIA)♦ President Organization Gestosis (2010)♦ Secretary General Organization Gestosis♦ FOGSI representative to AOFOG 2014-15♦ Convener “Save the Mother & Newborn National Initiative”♦ Elected member of Maharashtra Medical Council♦ Invited Member of National Commission on Population under chairmanship of Hon’ble Prime Minister of India.♦ Chairman of Ethics Committee, State Medical Council♦ Member of Ethics Committee, Medical Council India♦ Chairman of ICMR Technical Research Committee♦ Awarded many national prizes for his various presentationsProfessional Positions Held:-♦ Honorary Professor and Post-Graduate Teacher at B. J. Medical College and Sassoon General Hospitals, Pune Maharashtra, India♦ Honorary General Secretary, The Indian College of Obstetricians and GynecologistsInterests: ♦ Reproductive Endocrinology.♦ Post-Graduate Teaching.♦ High Risk Obstetrics


♦ He has published more than 60 national & international research papers♦ He has written books & chapters in many textbooks♦ He has given orations & guest lectures in more than 100 societies all over India & across the world

W9-2. Management of preeclampsia (PE) in Japan.

Taichi AkahoriDepartment of Obstetrics and Gynecology, Saitama Medical Center/ Saitama Medical University

Preeclampsia (PE) is a syndrome characterized by the onset of hypertension and proteinuria after 20 weeks of gestation. Dysgenesis of placentation in early pregnancy may result in relative placental hypoperfusion, which leads to release of antiangiogenic factors that alter maternal systemic endothelial function and induces symptoms of PE.In the management of PE, it is important to control blood pressure (BP) at appropriate level to prevent maternal and fetal complications. It is assumed that risk of eclampsia and cerebrovascular disorder increases when systolic BP exceeds 180mmHg, or diastolic BP exceeds 120mmHg. However, excessive suppression of BP may cause an iatrogenic dysfunction of feto-placental circulation. Although there is no established evidence for the extent of BP reduction, it is recommended to decrease 15% of mean arterial BP or to suppress severe hypertension to mild level.In Japan, hydralazine and methyldopa have been widely used as antihypertensive agents for PE, in spite of their insufficient hypotensive effect, just because sufficient experience of administration to hypertensive pregnant women. Only intravenous nicardipine (calcium-channel blocker) had been approved for PE patients with informed consent. It was just two years ago that nifedipine and labetarol were approved for pregnant women, so there are few reports in Japan for Ca blockades or α-β blockades comparing with foreign countries. We review our challenge and outcome in the management of PE with before-mentioned limitation in Japan.

Career history:• 4/1997-3/2003 - Medical student of Saitama Medical University• 4/2003-3/2005 - Resident of Department of Obstetrics and Gynecology, Saitama Medical Center / Saitama Medical University• 4/2005-3/2009 - Graduate school of Saitama Medical University - Saitama• 5/2006-4/2008 - Research student of Tokyo Medical and Dental University Department of Physiological Chemistry – Tokyo• 4/2010. Received a doctorate• 5/2009 - Assistant professor of Saitama Medical University Saitama Medical center / Department of Obstetrics and Gynecology - Saitama

W9-3. Antihypertensive drugs for pregnancy induced hypertension

Yoshikatsu Suzuki1, Ayano Matsuura1, Tomoe Arakawa1, Tamao Yamamoto2

1Nagoya City West Medical Center 2Mammy Rose Clinic

Drug therapy for pregnancy induced hypertension (PIH) should be started at a blood pressure (BP) of severe hypertension ( ≥ 160/110mmHg). When selecting antihypertensive drugs for hypertension during pregnancy, methyldopa, hydralazine, labetalol or nifedipine after week 20 of pregnancy should be selected as a first-choice drug. When systolic BP is ≥ 180mmHg or diastolic BP is ≥ 120mmHg was shown in pregnant or postpartum women, antihypertensive drugs for intravenous injection should be started under a diagnosis of hypertensive emergency. Two representative hypotensors, labetalol and nicardipine will be introduced in this work shop.Labetalol, αβ-blocker has been be useful for managing BP in pregnant women complicated by severe hypertension in world wide. It can also be used by revise of the package inserts since June 2011 in Japan.Thirty four pregnant women shown severe hypertension (16 preeclampsia; PE and 18 gestational hypertension; GH) were given oral labetalol 300-400mg daily. Fifteen were shown to be decrease in BP, more than 10% (effective), while 19 were less than 10% (ineffective) on 3rd day after administration. It was significant effective in GH (11/18) compared with that in PE (4/16, P = 0.02). The clinical symptoms disappeared in both group. The unfavorable changes in fetal heart rates was seen in 3 (1 for effective and 2 for ineffective).Postpartum women after cesarean section showed systolic BP ≥ 160mmHg, including 9 women complicated by hypertensive emergency were given by intravenous administration of nicardipine at 1-6mg/hr. Their BP subsequently could be stabilized under 160mmHg.


Yoshikatsu Suzuki, MD. Ph.D.CURRICULUM VITAEMay 2014PERSONAL BACKGROUNDBirthdate and place of birth: August 25, 1958, Aichi, JapanPresent address and telephone number: Nagoya City West Medical Center Department of Obstetrics and Gynecology Hiratecho1-1-1, Kitaku, Nagoya, 462-8508, JapanIntroduce myselfI graduated Nagoya City University (NCU) and had been belonging to Department of OB/GYN at NCU since 1986. I was appointed for Research Associate in OB/GYN in 1993. Since 1996, I have been studying the pathophysiology of preeclampsia, focusing on the vascular endothelial function seen in preeclampsia in Department of Pharmacology in NCU. I found that reduction of nitric oxide action might be not due to reduced production but reduced action of NO-cGMP pathway (J Physiol 2000), while a decrease in prostacyclin production was seen in the resistance artery obtained from preeclamptic women. (J Physiol 2002). Furthermore, it was found that administration of L-arginine plus folic acids could improve the reduced of NO action seen in animal model (Br J Pharmacol. 2005). Similarly, the administration in high risk women might prevent onset of preeclampsia due to improvement of the endothelial dysfunction. Now, I am interested in 24-h ambulatory blood pressure monitoring and the management of hypertension during pregnancy and postpartum.EDUCATION BACKGROUND1981 - 1986 Nagoya City University Medical Sciences1996 Earned PhD on medicine at Nagoya City University.UNIVERSITY APPOINTMENTS1993 - 2000 Nagoya City University Medical Sciences, Research Associate in Department of OB/GYN.2000-2010 Nagoya City University Graduate School of Medical Sciences in Department of OB/GYN,

Associate Professor2010-present Nagoya City West Medical Center, the 2nd in Development of OB/GYN, directorORGANIZATIONS AND SOCIETIESJapan Society for the Study of Hypertension in Pregnancy, 1990-present

W9-4. A novel pharmacotherapy of preeclampsia

Nobuyuki TakahashiTohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan

Pre-eclampsia (PE) is an important cause of maternal and fetal deaths due to pregnancy. The only definitive treatment to save their lives is to deliver the baby and the placenta, which results in a premature baby. Anti-hypertensives acceptable for use during pregnancy help control maternal blood pressure in PE, but they often reduce the blood supply to the placenta and the baby, leading to fetal growth restriction. This is most likely because these anti-hypertensives do not correct abnormalities specific to PE (which include high plasma levels of placentally-derived sFlt-1 and endotheliosis). We and other investigators have demonstrated that endothelin (ET-1) plays an important role in the pathogenesis of PE, and that antagonists of the endothelin type A receptor (ETAR) greatly ameliorate the PE-like condition that develops in rodents with experimentally induced excess sFlt-1. Unfortunately, ETAR antagonists are teratogenic and consequently unacceptable for use in treating PE. However, nicotinamide, a naturally occurring widely used amide of vitamin B3, is a potential non-teratogenic alternative because it relaxes blood vessels constricted with endothelin. The effects of nicotinamide on a PE-like condition in mice will be discussed.

Nobuyuki Takahashi, M.D., Ph.D.Associate ProfessorTohoku University Graduate School of Pharmaceutical SciencesDr. Nobuyuki Takahashi is a physician scientist and a nephrologist. After finishing the PhD program at Tohoku University, Dr. Takahashi moved to The University of North Carolina at Chapel Hill as a postdoctoral research associate. With Dr. Oliver Smithies, the Nobel Laureate who established gene targeting, Dr. Takahashi has generated several lines of genetically modified mice to study the roles of kidney on blood pressure regulation. Dr. Takahashi stayed at the same institute for about 14 years until he moved back to Tohoku University right before the earthquakes. Dr. Takahashi’s research is focused on the roles of genes regulating blood pressure on pregnancy-induced hypertension, diabetic kidney disease, and the metabolic syndrome. Most recently he is exploring novel pharmacotherapies of preeclampsia, kidney diseases and obesity. (129, 200 max)


W9-5. Increased placental expression of cannabinoid receptor 1 in preeclampsia

Attila MolvarecFirst Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary

Objective: The endocannabinoid system plays a key role in female reproduction, including implantation, decidualization and placentation. In the present study, we aimed to analyze cannabinoid receptor 1 (CB1), CB2 and fatty acid amid hydrolase (FAAH) expressions and localization in normal and preeclamptic placenta, in order to determine whether aberrant endocannabinoid activity is related to preeclampsia.Methods: Eighteen preeclamptic patients and 18 normotensive, healthy pregnant women with uncomplicated pregnancies were involved in our case-control study. We determined CB1, CB2 and FAAH expressions by Western immunoblotting and immunohistochemistry in placental samples collected directly after Cesarean section.Results: CB1 expression measured by Western immunoblotting was significantly higher in preeclamptic placenta, and these findings were confirmed by immunohistochemistry. CB1 immunoreactivity was markedly stronger in syncytiotrophoblasts, the mesenchymal core, decidua, villous capillary endothelial and smooth muscle cells, as well as in the amnion in preeclamptic samples compared to normal pregnancies. However, we did not find significant differences between preeclamptic and normal placenta in terms of CB2 and FAAH expressions and immunoreactivity.Conclusions: We observed markedly higher expression of CB1 protein in preeclamptic placental tissue. Increased CB1 expression might cause abnormal decidualization and impair trophoblast invasion, thus being involved in the pathogenesis of preeclampsia. As CB1 activation can induce endothelial dysfunction and enhance vascular inflammation, the strong CB1 immunoreaction in vascular endothelial and smooth muscle cells suggests that CB1 may contribute to the development of atherosis in the placental villi shown earlier in preeclampsia. While the detailed pathogenesis of preeclampsia is still unclear, the endocannabinoid system seems to play a role in the development of the disease.

W9-6. Recent pathophysiology of cell-free nucleic acid in pregnancy

Yuditiya Purwosunu

Dept of Obstetric Gynecology, University of Indonesia

The phenomenon of circulating cell-free DNA (cfDNA) is of importance for many biomedical disciplines. At present, cell-free DNA has been reported widely as promising noninvasive biomarkers for disease diagnosis and research. Recent years have witnessed some progress in the studies of the general characteristics of cell-free DNA, such as its concentration, extent of molecular weight, origin and existing forms, as well as in its clinical application. Biomarkers can be employed for screening for fetal genetic disorders, identifying individuals at sufficiently high risk for a confirmatory invasive procedure. Identification of cell-free fetal nucleic acids (DNA and RNA) in maternal plasma and the recognition that they represent a useful source of fetal genetic material for prenatal diagnosis has led to intensive efforts to develop non-invasive prenatal testing. This presentation summarizes the general characteristics and biological functions of cell-free DNA, recent developments in the field of non-invasive prenatal diagnosis through the use of cell-free fetal nucleic acids in maternal circulation during pregnancy and provides an overview of the possibilities for future clinical applications.

Yuditiya PurwosunuObjective

Save the life of fetal and mother, one at a time is my passion – through maternal fetal medicine.Work/Research ExperienceDes 2004-March 2005 Aceh Province Hospital, Sumatera – Obsgyn ward/OP chief at Regional Hospital. I am one of the survivor

of Asian Tsunami at that timeApril 2005- 2009. Showa University School of Medicine, Dept of Obstetrics Gynecology.2002 to 2005: The Eijman Molecular Biology Institute, Jakarta1999 to present: Dept of Obstetric and Gynecology, Faculty of Medicine, University of Indonesia, Jakarta. (Lecturer)2008 May: The Rescue Team for Myanmar: the cyclone disaster at Myanmar, represented Indonesia Health Team.2009 April-2012: Dept Genetics, FDD-MB. Kanazawa Medical University, Ishikawa, Japan (Post Grad Research on prenatal

diagnosis using fetal cells in maternal blood)2009-2010 Dept. Obstetrics Gyncology NCCHD (National Centre for Children Health and Development), Fetal Teraphy and

Intervention Division, Tokyo, Japan2010 to 2011:Fetal Maternal Foundation, Harris Birthright Center for Fetal Reseach Unit, King’s College Hospital, London2011 Necker Hospital, Fetal Therapy Division (TTTS), Paris, France

Education


1999 – 1999 MD - Univ. Indoensia2000 – 2004 Obstetrics Gynecology Specialist - Univ. Indonesia2005 – 2012 PhD - Dept Obstgyn. Showa Univ. School of Medicine2010 Des Dept. Obstetrics Gyncology NCCHD (National Centre for Children Health and Development), Fetal Teraphy

and Intervention Division, Tokyo, Japan2010 – 2011 Fetal Maternal Foundation, Harris Birthright Center for Fetal Reseach Unit, King’s College Hospital, London2011 Aug Necker Hospital Paris2011 – Now FDD-MB Kanazawa Medical Univ.2018 – 2014 Biomedics Doctoral Programme

PublicationPaper in peer reviewed international journals (31)Chapter of international published book (3)

Research Interest• Prenatal Diagnosis (fetal cell-free DNA and fetal cell) and preeclampsia (fetal mRNA quantifi cation).• Maternal Fetal Medicine through fetal therapy and intervention• Lowering maternal mortality and morbidity• Fetal Theraphy and Intervention

Awards/ScholarshipTakeda Scientifi c Foundation Scholarship (2005-2007)Showa Univ. Scholarship (2005)Ichiro Kanehara Foundation Scholarship (2007)Symposist Awards at Japan Association of Obstetrics Gynecology (JAOG) Meeting 2007FDD-MB Cluster Scholarship (2009 – 2012)Award at SGI Preeclampsia meeting, Sendai, Japan (2009)Young Ivestigator Award at ISSHP Meeting in Melbourne, Australia (2010)Travel Grant Award ISSHP Meeting 2011Grant from Fetal Maternal Foundation, Harris Birthright Unit, King’s College Hospital, London (2010)Shan S. Ratnam – Young Gynaecologist Award (2011), Taipei, Taiwan at AOCOG meetingYoung Scientist Award (2013), Bangkok at AOCOG meeting 2013


W10-1. Arrested lineage progression of oligodendrocytes with minor damage in the corticospinal tracts in developmental white matter injury model rat

Hideki HidaDept. Neurophysiol. & Brain Sci., Nagoya City Univ Grad Sch Med Sci, Nagoya 467-8601, Japan

Developmental white matter injury (DWMI) caused by hypoxia-ischemia (H-I) is associated with permanent neurodevelopmental disabilities such as motor and cognitive defi cits in preterm infants. As selective vulnerability of oligodendrocyte (OL) progenitor cells (OPCs) was reported in some case of DWMI, we made a DWMI model rat that was made by H-I (right common carotid artery occlusion followed 6% hypoxia for 1 hour) at P3. Impaired motor function especially in the hindlimb was shown in this model. To investigate pathological relevance to functional defi cits in this model, we investigated the pattern of cellular degeneration, counted the number of OL lineage cells and checked neuron damage after H-I. Active-caspase3/NeuN double-positive apoptotic neurons were not detected in the cortex. Detection of OL lineage markers revealed that NG2 positive cells increased in the ipsilateral WM at 2 day and PDGFRα positive cells increased at 7 day after H-I. Mature APC-positive OL decreased by 84 ± 2.45 % (n = 4) at 6 month later. Data suggest that cell death in the corticospinal neurons were not directly induced by H-I but arrested OL lineage progression with indirect minor damage of the neurons were induced in DWMI model rat. In addition, we will report our challenge in cell transplantation of mouse iPS cell-derived OPCs to DWMI model rat.

CURRICULUM VITAENAME: Hideki Hida, M.D., Ph.D.DATE OF BIRTH: July 11, 1965EDUCATION: 1985-1991, Medical School Nagoya City University Medical School, Japan. 1991-1995, Graduate School Department of Physiology Nagoya City University Medical School, Japan 1995-1997 Postdoctoral fellow Department of Neurology


The University of Chicago 1997-2001 Research associate Department of Physiology Nagoya City University Medical school, Japan 2001-2003 Assistant Professor Department of Physiology Nagoya City University Medical School, Japan 2003-2009 Associate Professor Department of Neuro-physiology & Brain Sciences Nagoya City University Grad School of Medical Sciences, Japan 2009- Professor Department of Neuro-physiology & Brain Sciences Nagoya City University Grad School of Medical Sciences, Japan

W10-2. Current perspectives in hypoxic-ischemic encephalopathy in Japan

Masahiro HayakawaCenter for Maternal-Neonatal Care, Nagoya University Hospital

Hypoxic ischemic encephalopathy (HIE) is one of the most critical pathologic conditions in neonatal medicine. Despite HIE is important disease, there are few reports of the incidence of HIE. This may be due to the fact that establishing a diagnosis of HIE may be challenging because infants may present with non-specific symptoms and HIE is not always caused by a sentinel event. Further, in some cases, an obvious hypoxic-ischemic event may have not been apparent during the intrapartum period or immediately after birth. Because of the diagnostic difficulty, neonatologists and obstetricians are not always able to recognize brain insult in infants who suffer partial asphyxia at birth. Therefore, the incidence of HIE might be underestimated.Hypoxic ischemic brain injury secondary to birth asphyxia can result in the development of cerebral palsy. Some publications have reported predictive factors for neurodevelopmental outcome in infants with HIE. Electroencephalography (EEG), magnetic resonance imaging (MRI), and laboratory data at birth are useful tools for predicting outcome based on neonatal risk factors. Whereas maternal and antenatal factors may foretell the development of HIE, these variables do not predict mortality or neurodevelopmental outcome.This lecture highlights current perspectives in HIE in Japan based on nationwide surveillance.

Masahiro Hayakawa, M.D., Ph.D.Division of Neonatology, Center for Maternal-Neonatal CareNagoya University Hospital65 Tsurumai-cho Showa-ku, Nagoya,466-8560, JapanE-mail: [email protected]: + 81 52 744 2294 FAX: + 81 52 744 2974WORK EXPERIENCECenter for Maternal-Neonatal Care, Nagoya University Hospital October 2001 - presentDepartment of Neonatology, Ogaki Municipal Hospital April 1997 - September 2001Department of Pediatrics, Nagoya University Hospital October 1993 - March 1997Department of Neonatology, Ogaki Municipal Hospital April 1992 - September 1993Department of Pediatrics, Toyota Memorial Hospital October 1990 - March 1992Department of Pediatrics, Nagoya University Hospital April 1990 - September 1990Department of Pediatrics, JA Aichi Kouseiren Kamo Hospital April 1989 - March 1990Resident, JA Aichi Kouseiren Kamo Hospital May 1988 - March 1989EDUCATIONSchool of Medicine, Mie University April, 1982 - March, 1988LANGUAGE SKILLSJapanese (native)English (basic speaking and reading)


W10-3. Trends in perinatal brain damage in our population-based study

Hiroshi SameshimaProfessor and Chairman, Department of Obstetrics and Gynecology, University of Miyazaki

Objective: Trends in cerebral palsy was investigated in a regional population-based study (PBS) in southern Japan where the perinatal mortality has been the world lowest.Materials and methods: From 1998, we performed a PBS on perinatal deaths and neonatal brain damage in Miyazaki District in which we have 10,000 deliveries annually. High risk infants were reported by 7 regional secondary centers on a voluntary basis, which presumably covers 90-95% of handicapped infants according to our previous study. Two consecutive 5-year periods (2001-2005, 2006-2010) were compared.Results: Each period had 51,000 deliveries. Fetal deaths decreased (157 to 136), so did neonatal deaths (79 to 47), infantile deaths (163 to 119) and brain-damaged infants (126 to 88), where all changes reached statistically significant (Chi square test, p < .05). Among the infants with brain damage, term infants decreased while preterm infants (26 to 36 weeks of gestation) increased. The most contributing factors to these changes were a decrease in asphyxia at term and an increase in PVL at preterm. However, unknown causes or multiple causes were still existed.Conclusion: Our regional PBS reveals that the perinatal mortality and infantile mortality has decreased significantly with a significant decrease in the incidence of brain damage. This trend is true with term infants, but not with preterm infants.

Dr. Hiroshi Sameshima is an outstanding clinician scientist in Maternal-Fetal Medicine. He received his MD from Kagoshima University, Japan, in 1981. He was trained in Obstetrics and Gynecology in Kagoshima City Hospital and in the subspeciality there. He received research training in fetal physiology at Loma Linda University, California, USA, between 1983 and 1986. He received his PhD in 1991 regarding hypoxemic inhibition of fetal breathing movements in goats.Dr. Sameshima is currently Professor and Chairman, Department of Obstetrics and Gynecology in University of Miyazaki, Japan. He has served or is serving in many committees related to maternal-fetal medicine, for instance, in Japan Society of Obstetrics and Gynecology, Japan Society of Maternal-Fetal Medicine, Japan Society of Perinatal-Neonatal Medicine and so on. He is also a committee member of Japan Council for Quality Health Care where a population-based study on cerebral palsy has been on-going.Dr. Sameshima’s research focuses are FHR monitoring, gestational diabetes mellitus, fetal behavior, hypoxia and brain damage, a regional population-based study in his research field, and so on.

W10-4. The Japan obstetric compensation system for cerebral palsy

Takashi OkaiDirector, Imperial Gift Foundation, Maternal and Child Health Center Aiiku Hospital

It is usually difficult to determine malpractice in cases of medical accidents during delivery, and these cases are often contended in court. The frequency of such disputes is one of the reasons for the shortage in Obstetricians.In order to maintain an environment that can, in part, provide Obstetric care without worry, we have launched the Japan Obstetric Compensation System for Cerebral Palsy (JOCSCP).Basic concept of JOCSCP includes two parts, those are “compensation” and “analysis of causes & measures to present future cases”. Persons eligible for compensation are children with severe cerebral palsy related to brain injuries during delivery. For nursing care expenses, total monetary compensation of 30 million yen is provided to the families of CP babies in the installment way.As of May 2013, 501 cases have been accepted and cause analyses completed in 319 cases. The most frequent cause of CP was abruption placenta which covered about 25% of all cases and the second was cord compression, but we found other various factors related to CP.Both medical provide side and patient side showed the opinion that they consented the reports from cause analysis committee in more than 70% of the cases.After launching JOCSCP, the litigation rate has been deceased.The detailed date will be presented in the presentation of the congress.

CURRICULUM VITAENAME: Takashi OkaiDATE OF BIRTH: August 6, 1947, JapanPRESENT APPOINTMENT:

• Director of Imperial Gift Foundation Maternal and Child Health Center Aiiku Hospital• Visiting Professor of Dept. of OB/GYN, Showa University School of Medicine• Executive Board Member of The Japan Association of Medical Science

EDUCATION, RESIDENCY AND DOCTORATE:• Graduated from Faculty of Medicine, University of Tokyo in 1973• Resident in Dept. of OB/GYN, University of Tokyo Hospital, Aiiku Hospital and Nagano Red Cross Hospital, 1974-1978


• Obtained Degree of Ph D (Medical Science) from University of Tokyo, 1983PROFESSIONAL CAREER:

• Lecturer of Dept. of OB/GYN, University of Tokyo, 1979-1981• Chief of Dept. of OB/GYN, Sanraku Hospital, 1982-1983• Lecturer of Dept. of OB/GYN, University of Tokyo, 1983-1986• Assistant Professor of Dept. of OB/GYN, University of Tokyo, 1986-1992• Research Fellow at Loma Linda University California, USA, 1987-1988• Associate Professor and Vice-Chairman of Dept. of OB/GYN, University of Tokyo, 1993-1996• Vice-Director of Aiiku Hospital and Head of Dept. of OB/GYN, 1996-2000• Professor and Chairman of Dept. of OB/GYN, Showa University, 2000-2013• Head of Perinatal Center, Showa University Hospital, 2000-2013

W10-5. Analyses of 39 cases of cerebral palsy caused by placental abruption on the Japan obstetric compensation system for cerebral palsy

Keiya FujimoriDepartment of Obstetrics and Gynecology, School of Medicine, Fukushima Medical University

Placental abruption was the most common cause of cerebral palsy in 128 patients enrolled between January 2009 and June 2012 in the Japan Obstetric Compensation System for Cerebral Palsy, accounting for 39 cases. We analyzed these 39 cases.For the risk factors profile, 77% of these women were multiparous, 17% were smokers, and 10% were with preeclampsia, however no recurrent case was found.Two thirds of the patients developed placental abruption at home. One third of the patients were transferred to a tertiary hospital after diagnosis.The initial symptoms of the patients were abdominal pain in 62%, vaginal bleeding in 13%, and loss of fetal movement in 21%. Preterm labor was originally diagnosed in 44% and β2-stimulants were administered.Ultrasonography was performed in two thirds of the cases, of which 40% had retroplacental hematoma, 24% had placental thickening, and 28% had no abnormal findings. More than half of the patients had abnormal fetal heart rate, mostly bradycardia, on admission. Medians of the birth week and neonatal weight were 37.3 weeks and 2,522 g, respectively. The median decision-to-delivery interval was 39 minutes. Delivery in 85% of the cases was by cesarean section. Umbilical blood gas analysis was performed in 77%, and pH was less than 7.0 in all cases except one.The education of pregnant women on the initial symptoms of placental abruption (abdominal pain, vaginal bleeding, loss of fetal movement), recommending earlier consultations with the symptoms, and diagnosis by using cardiotocography and ultrasonography are important factors in decreasing cerebral palsy resulting from placental abruption.

ProfileName: FUJIMORI, KeiyaEDUCATION1992 Ph.D. Department of Obstetrics and Gynecology, School of Medicine, Fukushima Medical University1988 M.D. School of Medicine, Fukushima Medical UniversityPROFESSIONAL EXPERIENCE2009-present Professor and Chairman, Department of Obstetrics and Gynecology, School of Medicine, Fukushima Medical University,

Japan2007-2009 Associate Professor, Department of Obstetrics and Gynecology, School of Medicine, Fukushima Medical University,

Japan2002-2007 Assistant Professor, Department of Obstetrics and Gynecology, School of Medicine, Fukushima Medical University,

Japan1992-1994 Postdoctoral fellowship, Maternal Fetal Medicine, University of California, Irvine, USA



W11-1. What is the problem with echo screening for congenital heart disease?

Ryu MatsuokaDept. of Obstetrics and Gynecology, Showa University School of Medicine

Congenital Heart disease (CHD) is most common disease up to 1% with newborn baby, and has also much variation of disease and in severity. Therefor CHD has a big impact on the prognosis of newborn baby. It is clear fetal diagnosis of CHD is important. But it is not so easy. Objectives: The purpose of this study is to identify and remedy the problems of fetal cardiac scan and to explore an improvement in it. Methods: The clinical course and diagnosis of CHD except karyotype disorder in our department in 2000 - 2010 were reviewed retrospectively. All pregnant women undergo thorough ultrasound examination for fetus at 18~19 and 30 weeks of gestation or at the fi rst time of visit. The scan was performed according to our check up list.Result: The incident of CHD was 1.0% (111cases) in all deliveries (11,072 cases). The prenatal diagnosis rate of CHD was 47.7% (53/111). There were 31 in 45 cases, excludes fetal arrhythmia and small VSD (20 cases were referrals case). 14 cases could not be detected (5 pulmonary artery stenosis, 3 total anomalous pulmonary venous return, 2 tetralogy of Fallot, 1 corrected transposition of great arteries, 1disease transection of the aorta, 1 mitral stenosis, 1 pulmonary artery atresia). Seven cases of 14 had cyanosis after birth. Conclusion: CHD with obvious morphological defect can be detected regardless of special technic or way of ultrasound exam. However, only a screening test with 4CV ∙ 3VV is insuffi cient, in order to improve the detection rate of CHD. So, we need scan with building cross-section must be based on precise anatomical knowledge.

Curriculum VitaeName : Ryu Matsuoka, M.D., Ph.D.E-mail : [email protected] Backgrounds

Doctor of Medicine, 1994, University of Tsukuba school of Medicine and Medical science, Tsukuba, JapanProfessional Positions

PresentAssistant professor, Dept. of Dept. of Obstetrics and Gynecology, Showa University School of Medicine

SubspecialityPerinatology, Prenatal Diagnosis, Fetal therapy, High Risk Pregnancy

Academic Positions Held2014.6 – presentAssistant professor, Dept. of Dept. of Obstetrics and Gynecology, Showa University School of Medicine2009. 4 – 2014.5College lecturer, Dept. of Dept. of Obstetrics and Gynecology, Showa University School of Medicine2002.1 – 2009.3Readership of hospital ward, Dept. of Dept. of Obstetrics and Gynecology, Showa University School of Medicine

W11-2. Fetal echocardiography: cardiac function

Yuka YamamotoDepartment of Obstetrics and Gynecology, Juntendo University Faculty of Medicine

At fetal stage, the ventricular wall has original stiffness due to the immature myocardium with less calcium storage and random cell arrangement. In utero, right ventricle works more than the left which is equal to 60% of total combined cardiac output (CCO) in the right. With gestation, CCO increases exponentially from 210ml/min at 20 weeks to 1900ml/min at 38 weeks. Due to this dramatic change of fetal circulation before birth, it is important to know how to evaluate the fetal cardiac function with the limited tools.The simple way to evaluate fetal cardiac function is a two dimentional ultrasound such as cardiac thoracic ratio and m-mode to calculate the ejection fraction. Doppler assessments include infl ow Doppler (Tei index, isovolemic relaxation time (IVRT) and isovolemic contraction time (ICT)) and systemic venous Doppler (ductus venosus, inferior vena cava and umbilical vein). Indeed, we calculate the CCO in the fetus. Furthermore, tissue Doppler imaging and velocity vector imaging (VVI) also apply to evaluate the fetal cardiac function.At fi rst trimester, the stiffness of fetal heart is obvious with monophasic infl ow and longer IVRT& ICT. The atrial contraction is important and it seems to contribute the additional CCO. Impaired atrial contraction such as Ebstein’s anomaly is critical for fetuses to survive even fetal stage. Fetal echocardiogram can provide additional information to manage complicated fetuses as well as help to understand natural history of fetal circulation.


Yuka Yamamoto M.D., PhD.Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine2-1-1 Hongo, Bunkyo, Tokyo, JapanTel: + 81-3-3813-3111Fax: + 81-3-5689-7460

Education:1996-2002 M.D., Faculty of Medicine, Juntendo University School of Medicine, Tokyo2007-2010 Doctor Degree (PhD), Department of OB&GYN, Juntendo University Faculty of Medicine, TokyoMedical License:2002 Physician’s License in Japan (No.425677)2007 Japan Society of Obstetrics and Gynecology (No.20020079-N-0707)2013 Japan Society of Perinatal and Neonatal Medicine2014 Fetal Medicine Foundation certified in nuchal translucencyProfessional Training and Employment:Jan. 2014 Associate professor at the Department of OB&GYN, Juntendo University Faculty of Medicine, TokyoJan. 2012 Assistant professor at the Department of OB&GYN, Juntendo University Faculty of Medicine, TokyoOct. 2009 Clinical research fellow at the Department of Pediatric Cardiology, University of Alberta, CanadaOct. 2007 Post-doctoral fellow at the Department of OB&GYN, University of Alberta, Canadal2002- Trainee at the Department of OB&GYN, Juntendo University Faculty of Medicine, TokyoPublications: 1. Yamamoto Y, Thebaud B, Vadivel A, Eaton F, Jain V, Hornberger LK. Doppler parameters of fetal lung hypoplasia and impact of

sildenafil. Am J Obstet Gynecol. 2014 Mar. 2. Yamamoto Y, Khoo NS, Brooks PA, Savard W, Hirose A, Hornberger LK. Severe Left Heart Obstruction with Retrograde Arch Flow

Importantly Influences Fetal Cerebral and Placental Blood Flow. Ultrasound Obstet Gynecol. 2013:42(3):294-9 3. McBrien A, Howley L, Yamamoto Y, Hutchinson D, Hirose A, Sekar P, Jain V, Motan T, Trines J, Savard W, Hornberger L. Changes

in the Cardiac Axis from 8 to 14 + 6 Weeks of Gestation. Ultrasound Obstet Gynecol. 2013 4. Howley LW, Yamamoto Y, Sonesson SE, Sekar P, Jain V, Motan T, Savard W, Wagner B, Trines J, Hornberger LK. Antegrade Late

Diastolic Arterial Flow In The Fetus: Insight Into Fetal Atrial Function. Am J Obstet Gynecol. 2013 5. Yamamoto Y., Hornberger LK. Progression of outflow tract obstruction in the fetus. Early Hum Dev. 2012;88(5):279-85. 6. Tanaka S, Stock JS, Yamamoto Y, Kondejewski J, Olson DM. Understanding perinatal mortality. Obstetrics, Gynecology &

Reproductive Medicine 2010.08.004 7. Yamamoto Y, Olson DM, van Bennekom M, Brindley DN, Hemmings DG. Increased Expression of Enzymes for Sphingosine

1-Phosphate Turnover and Signaling in Human Decidua During Late Pregnancy. Biol Reprod. 2010; 82(3):628-35 8. David M Olson, Inge Christiaens, Sara Gracie, Yuka Yamamoto, Bryan F Mitchell. Emerging tocolytics: challenges in designing

and testing drugs to delay preterm delivery and prolong pregnancy. Expert Opin. Emerging Drugs 2008 13(4):695-707 9. Y. Yamamoto, N. Suga, T. Ujihira, S. Kusunoki, M. Maruyama, Y. Abe, F. Nagai, T. Taguchi, N. Abe, A. Tajima, M. Nojima, K.

Yoshida; Successful management of pregnancy associated aplastic anemia- A case of report- Chiba Journal of Obstetrics and Gynecology, 2008; 1: 42-46

10. Y. Yamamoto, N. Nishioka, Y. Shirai, T. Kida, Y. Katsumata, N. Abe, M. Awaji, I. Nagasawa, T. Yamamoto; Case report of acute purulent meningitis with pregnancy caused by Penicillin-resistant Streptococcus Pneumoniae(PRSP). Saitama Journal of Obstetrics and Gynecology, 2004; 34: 14-17

W11-3. Ultrasound screening of umbilical cord and perinatal outcomes

Junichi HasegawaDepartment of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan

Objective: To clarify the usability of ultrasound screening for predicting non-reassuring fetal status (NRFS) during labor.Methods: Prospective cohort study was conducted between 2012 and 2013. Ultrasound screening of placenta and umbilical cord abnormalities using check list were attempted at 36 weeks’ gestation. Subjects who were taken this ultrasound screening and not planned elective cesarean section (CS) were divided into three levels of groups according to the risk of NRFS. After delivery, frequencies of NRFS and emergency CS rate were compared among these risk groups. High risk was defined in cases with velamentous, marginal cord insertion on the lower uterus, three or more nuchal cords and/or hyper-coiled cord. Middle risk was defined in cases with the other velamentous insertion, moderate fetal growth restriction, twice nuchal cords, and/or single umbilical artery. The others were defined as low risk.Results: After exclusion of 111 cases of elective CS, 34 cases of high, 45 cases of middle and 600 cases of low risk were analyzed. NRFS was diagnosed in 17.6% (6/34) of high risk, 11.1%* (5/45) of middle risk and 6.2% (37/600) of low risk, respectively. Emergency CS was performed in 8.8% (3/34) of high risk, 4.4% (2/45) of middle risk, and 1.0% (6/600) of low risk, respectively (*p < 0.05 compared to low risk).Conclusion: Antenatal ultrasound screening of placental and umbilical cord abnormalities could identify cases of high risk delivery.


Junichi Hasegawa, M.D., Ph.D.Assistant professorDepartment of Obstetrics and Gynecology, Showa University School of Medicine

CAREER HISTORY2011-present Assistant Professor, Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan2009-2011 Bologna University, Bologna, Italy2006-2009 Assistant Professor, Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan2003-2006 Assistant Professor, Department of Obstetrics and Gynecology, Showa University Northern Yokohama Hospital,

Yokohama, Japan1998-2003 Resident, Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, JapanLICENSURE2011 Board Certified Specialist of the Japan Society of Perinatal and Neonatal Medicine2007 Board Certified Specialist of the Japan Society of Ultrasonics in Medicine2003 Medical Specialist of Obstetrics and Gynecology, Japan Society of Obstetrics and Gynecology1998 Medical Doctor’s License, Japan (No. 397183)PROFESSIONAL MEMBERSHIPSUltrasound in Obstetrics and GynecologyJapan Society of Obstetrics and GynecologyJapan Society of Perinatal and Neonatal MedicineJapan Society of Ultrasonics in MedicineJapan Society of Biomedical Engineering in Obstetrics and GynecologyJapan Society for Reproductive MedicineJapan Society of Human GeneticsAWARDS2014 Scientific Award of Japan Society of Obstetrics and Gynecology2005 Scientific Award of Japan Society for Reproductive Medicine

W11-4. Fetal bone dysplasia and analysis of pathophysiological mechanisms

Seiji TsutsumiDepartment of Obstetrics and Gynecology, Yamagata University, Faculty of Medicine

Fetal bone dysplasias are rare disorders. These conditions have been estimated to affect one in 100,000 newborns. In the present situation, no cure is known for almost of them, and it is not necessarily that the precise diagnosis contributes its treatment or improvement of prognosis. However, because they include some groups with poor life prognosis, it is clinically meaningful to diagnose precisely, predict neonatal prognosis, and prepare for perinatal management. For obstetrician, it is particularly important to manage the cases which comprise conditions that usually lead to death in utero, at or shortly after birth. For example, thanatopholic dysplasia is one of the neonatally lethal osteochondrodysplasia due to hypoplastic lung, but some patients with thanatophoic dysplasia have been kept alive into late childhood with continued intensive care. Osteogenesis imperfecta is increased lethality depending on sub-type.At our facility, we examined 13 fetal bone dysplasias for the past eight years. 10 cases were diagnosed prenatally by images of ultrasonography and/or X-ray 3-dimentional computed tomography. Furthermore, the causative gene mutations were identified in four cases of them. Under precise diagnoses using graphical imaging and genetic analysis, we could provide appropriate support including genetic counseling.

Seiji TsutsumiBiography:

1990 Graduated from Yamagata University Faculty of Medicine, School of medicine1995 Graduated from Yamagata University Faculty of Medicine, Graduate School of Medical Science. (Ph. D. in Medicine.)1995 Yamagata Prefectural Central Hospital1996 Nagai City Hospital1997 Yamagata Saisei Hospital2000 Yamagata University Faculty of Medicine, assistant professor2002-2004　New England Medical Center, Molecular Cardiology Research Institute (United States), postdoctoral fellow.2011 Yamagata University Hospital, associate professor

Memberships:Japan Society of Obstetrics and GynecologyJapan Society of Perinatal and Neonatal MedicineThe Japan Society of Human GeneticsThe Japan Society of Ultrasonics in Medicine

W1-1. Exosomal signalling in complications of pregnancy

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