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First Trimester Assessment of Ductus Venosus in Screening for Fetal Chromosomal and Cardiac Defects

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First Trimester Assessment of Ductus Venosus in Screening for Fetal Chromosomal and Cardiac Defects First trimester assessment of ductus venosus in screening for fetal chromosomal and cardiac defects Valoración del ductus venoso en el primer trimestre en el cribado de anomalías cromosómicas fetales y defectos cardiacos Nerea Maiz Elizaran ADVERTIMENT. La consulta d’aquesta tesi queda condicionada a l’acceptació de les següents condicions d'ús: La difusió d’aquesta tesi per mitjà del servei TDX (www.tesisenxarxa.net) ha estat autoritzada pels titulars dels drets de propietat intel·lectual únicament per a usos privats emmarcats en activitats d’investigació i docència. No s’autoritza la seva reproducció amb finalitats de lucre ni la seva difusió i posada a disposició des d’un lloc aliè al servei TDX. No s’autoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant al resum de presentació de la tesi com als seus continguts. En la utilització o cita de parts de la tesi és obligat indicar el nom de la persona autora. ADVERTENCIA. La consulta de esta tesis queda condicionada a la aceptación de las siguientes condiciones de uso: La difusión de esta tesis por medio del servicio TDR (www.tesisenred.net) ha sido autorizada por los titulares de los derechos de propiedad intelectual únicamente para usos privados enmarcados en actividades de investigación y docencia. No se autoriza su reproducción con finalidades de lucro ni su difusión y puesta a disposición desde un sitio ajeno al servicio TDR. No se autoriza la presentación de su contenido en una ventana o marco ajeno a TDR (framing). Esta reserva de derechos afecta tanto al resumen de presentación de la tesis como a sus contenidos. En la utilización o cita de partes de la tesis es obligado indicar el nombre de la persona autora. WARNING. On having consulted this thesis you’re accepting the following use conditions: Spreading this thesis by the TDX (www.tesisenxarxa.net) service has been authorized by the titular of the intellectual property rights only for private uses placed in investigation and teaching activities. Reproduction with lucrative aims is not authorized neither its spreading and availability from a site foreign to the TDX service. Introducing its content in a window or frame foreign to the TDX service is not authorized (framing). This rights affect to the presentation summary of the thesis as well as to its contents. In the using or citation of parts of the thesis it’s obliged to indicate the name of the author. Departament d’Obstetricia i Ginecologia, Pediatria, Radiologia i Anatomía Programa de doctorat: Obstetricia i Ginecologia, Bienni: 1999-2001 0A0&&4H 64H&A&8 Para aspirar al grado de Doctora en Medicina y Cirugía con Mención de Doctor Europeo Enero 2010 Director: Professor Kypros Herodotou Nicolaides King’s College and University College, University of London, England Tutor: Profesor Eduard Gratacós Solsona Universitat de Barcelona, Spain 1 Departament d’Obstetricia i Ginecologia, Pediatria, Radiologia i Anatomía Programa de doctorat: Obstetricia i Ginecologia, Bienni: 1999-2001 Submitted by 0A0&&4H 64H&A&8 For the degree of European Doctor in Medicine January 2010 Supervisor: Professor Kypros Herodotou Nicolaides King’s College and University College, University of London, England Tutor: Professor Eduard Gratacós Solsona Universitat de Barcelona, Spain 3 Professor Kypros Herodotou Nicolaides King’s College and University College, University of London, England I confirm that Dr Nerea Maiz Elizaran has carried out under my supervision the studies presented in the Thesis: First trimester assessment of ductus venosus in screening for fetal chromosomal and cardiac defects I have read the Thesis and I am happy for this to be presented to the Tribunal for The Degree of European Doctor in Medicine Professor Kypros Herodotou Nicolaides London October 2009 5 Al aita y a la ama 7 ACKNOWLEDGEMENTS 8264B3 Thanks to Professor Nicolaides, it is difficult to explain in a few words how grateful I am. He taught me patiently, guided me during three years and was the best example of hard work, generosity and enthusiasm. Thanks for giving me a chance. Thanks for sharing the passion for Fetal Medicine. To Professor Eduard Gratacós, tutor of this thesis, for his advice and availability. Thanks to all the Research Fellows of the Harris Birthright Research Centre, for all the work and for being “my family” during three fantastic years. Without you this would have been impossible. To Katy, Catalina, Francisca, Walter, Themis, Nicola, Ebru, Ranjit, Marisa, Ismini,...... we shared so many things!! thanks for all the support and being my best friends. To the midwifes, to July, for making our lives easier. To the consultants, for being so patients. Thanks to my parents and brothers for all the love and support. I owe them what I have and what I am. Thanks for being so close despite the distance. To my friends and colleagues at Institut Dexeus and Sant Joan de Déu hospital in Barcelona, where I learned so many things about Obstetrics, about Fetal Medicine, ...but also about life! To Inés, Maite, Pilar, Yeli, Juanjo, for their friendship and great years in Barcelona. To Luis, I wish you were here to share this moment with you. Thanks to my colleagues at Clínica del Pilar in San Sebastian for trusting me. To Juana, Sofia, Cristina, Leyre, Ana, Esther, Maria,...for their unconditional friendship. 9 ACKNOWLEDGEMENTS @&84B3 Gracias al Profesor Nicolaides, es difícil expresar en pocas palabras todo mi agradecimiento. Él me enseñó y guió durante tres años, y fue el mejor ejemplo de trabajador incansable, generosidad y entusiasmo. Gracias por darme una oportunidad. Gracias por compartir la pasión por la Medicina Fetal. Al Profesor Eduard Gratacós, tutor de esta tesis, por sus consejos y disponibilidad. A los research fellows del Harris Birthright Research Centre, por todo su trabajo y por ser mi “familia” durante 3 años fantásticos. Sin ellos esta tesis hubiera sido imposible. A Katy, Catalina, Francisca, Walter, Themis, Nicola, Ebru, Ranjit, Marisa, Ismini,… hemos compartido tantas cosas!!! Gracias por todo el apoyo y ser mis mejores amigos. A las “midwifes”, a July, por hacer nuestra vida más fácil. A los “consultants” por su paciencia. A mis padres y mis hermanos, gracias por todo el amor y el apoyo constante. A ellos les debo lo que tengo y lo que soy. Gracias por estar tan cerca a pesar de la distancia. A mis amigos y compañeros del Institut Dexeus y el Hospital Sant Joan de Déu donde aprendí Obstetricia, Medicina Fetal,…y aprendí de la vida!. A mis amigos Inés, Maite, Pilar, Yeli, Juanjo por su amistad y los fantásticos años en Barcelona. A Luis, ojalá estuvieras aquí para compartir este momento contigo. Mi agradecimiento a mis compañeros de la Clínica del Pilar de San Sebastián por confiar en mí. A Juana, Sofía, Cristina, Leyre, Ana, Esther, María,.. por su amistad incondicional. 10 11 CONTENTS INDEX PAGES ABBREVIATIONS 17 19 1.1 DUCTUS VENOSUS 21 1.1.1 Anatomy 21 1.1.2 Functional anatomy 21 1.1.3 Ductus venosus shunting 23 1.1.4 Doppler assessment of the ductus venosus 24 Quantitative assessment of the ductus venosus waveform: velocities and indexes 25 Qualitative assessment of the ductus venosus waveform Reproducibility 27 1.2 DUCTUS VENOSUS AND CHROMOSOMAL ABNORMALITIES 28 1.2.1 Overview 28 1.2.2 Assessment of risk for chromosomal abnormalities 28 Background or a priori risk 28 Maternal age and gestation 28 Fetal nuchal translucency 31 Maternal serum biochemistry 31 1.2.3 Abnormal flow in the ductus venosus 32 1.3 DUCTUS VENOSUS AND CARDIAC DEFECTS 33 1.3.1 Overview 33 1.3.2 Prevalence of congenital cardiac defects 34 1.3.3 Screening for fetal cardiac defects 35 Family history of congenital cardiac defects 35 Maternal diabetes mellitus 35 Maternal ingestion of known teratogens 36 13 Screening through risk factors in the maternal history 38 Screening by nuchal translucency 38 1.3.4 Ductus venosus and cardiac defects 39 1.4 DUCUS VENOSUS AND FETAL GROWTH RESTRICTION (FGR) 40 1.4.1 Overview 40 1.4.2 Diagnostic approach to FGR 41 1.4.3 FGR due to placental insufficiency 43 Fetal cardiovascular changes 44 Fetal biophysical changes 45 Antenatal surveillance of FGR due to placental insufficiency 45 1.4.4 Role of the ductus venosus in FGR 47 1.5 DUCTUS VENOSUS AND ADVERSE PREGNANCY OUTCOME 48 1.5.1 Pregnancy loss 48 First trimester screening for pregnancy loss 48 Ductus venosus in the first trimester and pregnancy loss 50 1.5.2 Major abnormalities 51 First trimester screening for major abnormalities 51 Screening for major abnormalities by nuchal translucency 52 Screening for major abnormalities by ductus venosus flow 53 1.6 DUCTUS VENOSUS AND TWIN PREGNANCIES 54 1.6.1 Overview 54 1.6.2 Pregnancy complications in twins 55 Selective FGR in monochorionic twins 56 1.6.3 Twin to twin transfusion syndrome (TTTS) 57 Role of the ductus venosus flow in TTTS 58 Prediction of TTTS 59 1.6.4 Screening for chromosomal abnormalities in twin pregnancies 60 Screening by maternal age 60 Screening by nuchal translucency 60 Screening by maternal serum biochemistry 61 Amniocentesis and CVS in twin pregnancies 61 14 1.7 HYPOTHESIS OF THE THESIS 62 1.8 AIMS OF THE THESIS 62 65 STUDY 1 69 Maiz N, Kagan KO, Milovanovic Z, Celik E, Nicolaides KH. Learning curve for Doppler assessment of ductus venosus flow at 11-13 weeks. Ultrasound Obstet Gynecol 2008;31:503-6. STUDY 2 75 Maiz N, Plasencia W, Dagklis T, Faros E, Nicolaides KH. Ductus venosus Doppler in fetuses with cardiac defects and high nuchal translucency thickness. Ultrasound Obstet Gynecol 2008;31:256-60.
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