memoria 2011
2011
annual report
Research in maternal-infant health ClĂnic Barcelona Fetal and Perinatal research Team
Abril 2012
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ANNUAL REPORT 2011
ANNUAL REPORT 2011
welcome
SUMMARY
Dear Friends, Another year has passed, and you have in your hands the memory of our Research Team in Fetal and Perinatal Medicine. During 2011 we have made some progress in key areas for future consolidation of the Fetal Medicine Centre, working to realize an increasingly professional structure that is required by the high-level scientific research. To that end, we have joined the management team profiles for economists and financial analysts, which has been an indispensable complement to the scientific growth. In addition, it has clearly shaped the architecture of our lines of research, which also now have a common supra-structure of platforms.
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Who we are
What we do Experience, Goals, Research Grants
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Leader in specialized training center
Diffusion. Presence in the media
Acknowledgements
During this year our Research Team has been awarded a total of five new research projects and a dozen scholarships to our post-doctoral researchers, putting in the hands of our dedicated team more resources to move towards such important challenges as discovering biomarkers for the brain and new methods of diagnosing cardiovascular health in fetal life, as well as getting a better and more refined understanding of intrauterine growth restriction. In the following pages you will find more information about each of our lines of research. Our current financial situation is uncertain, but we have the talent and ambition to continue growing in the pursuit of excellence. We have a strong team of researchers and we look to incorporate backgrounds that contribute to strengthening international competitiveness and making the center even more multidisciplinary. As you know, our organization aims to bring research advances to our society, so we are dramatically increasing direct contact with patients. In November we organized a meeting in Barcelona attended by over 120 families, a key part to advancing our research work. Also we participated in a rally in London along with our partner and British financier CEREBRA. Again, of course, it is necessary to acknowledge the continued support of patients, donors and funders, which allow our team to continue growing steadily. All supporters are addressed in this summary.
EDUARD GRATACĂ“S
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Fetal and Perinatal Research Team
Fetal and Perinatal Research Team
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ANNUAL REPORT 2011
ANNUAL REPORT 2011
WHOWEARE
Fetal and Perinatal Research Team
Our mission Our center works to find solutions to diseases with prenatal origin. To accomplish this, a multidisciplinary team consisting of experts in Maternal-Child Care and Neonatology apply different methods in order to develop new technology and techniques that allow for early diagnosis and new therapy techniques. With a functional design, we integrated prenatal and postnatal care so that the fetus and child are considered the same patient monitored over a longer period of time, a not-sousual design that has received several awards.
Human Resources In 2011 our team has grown from a staff of 10 to over 60 people, including clinicians, neuropsychologists, epidemiologists, biologists, statisticians, bio-engineers, nurses and research assistants. In addition, we host residents in their last year of preparation at both national and international universities, as well as fourth year medical students and telecommunications engineers in their last year of study. Our Research Team holds a principle of equal opportunity which appears in each of the areas that operates, from selection and recruitment processes, through wage policy, to education and conciliation. We also promote non-discriminatory communication and transparency, both internally and externally.
Addressing the same problem from different angles can overcome scientific and technological challenges.
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Fetal and Perinatal Research Team
Structure
Organization
Our Research Team is part of the Hospital Clinic de Barcelona and IDIBAPS. Hospital Clinic de Barcelona is a tertiary university hospital with more than 100 years of experience. It provides care in practically all medical specialties, including surgery and mental health, with a capacity of more than 900 beds. It is a national and international reference center in various lines of medical care, research, innovation, and quality education, excelling in scientific production. The activity related to hospital care activity is internally divided into institutes. Dr. Eduard Gratacos, who is Head of our Research Team, also serves as the Head of the Institute of Gynecology, Obstetrics, and Neonatology (ICGON).
The operations relating to research, cross platforms, laboratories, and administrative management of the equipment are located at Hospital Maternity Clinic Headquarters. Also, thanks to some alliances and partnership contracts, animal experimentation is conducted on the premises of the Faculty of Pharmacy, University of Barcelona and the Hospital Sant Joan de DĂŠu. Finally, magnetic resonance imaging (MRI) is performed at the headquarters of Hospital Clinic de Barcelona.
The Institute of Biomedical Research August Pi i Sunyer (IDIBAPS) is the first Health Research Institute accredited by the National Health System as having a scientific output that is among the largest in Europe. Finally, the administrative management of the research team is in the hands of the Clinic Foundation for Biomedical Research (FCRB).
Fetal and Perinatal Research Team
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ANNUAL REPORT 2011
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OUR RESEARCH WORK 5 lINES The main objective is to identify those diseases that originate in the prenatal stage and leading to a poor quality of life in children and adults. It has been shown that this problem particularly affects the heart and brain during development.
WHATWEDO experienciE
challenges
For years we have developed innovative technology that has advanced the understanding of how the brain and heart are “reprogrammed” in fetuses with certain complications. These technological endeavors include:
For this reason, the work during the next few years will focus on a large transdisciplinary project to study prenatal brain and heart problems at all levels in order to provide new techniques for clinical practice and to benefit society at large. Our future proposal focuses on:
Obtaining new technologies and treatment for brain and heart “reprogramming”. Models for restriction of oxygen to safely assess damage to the brain and heart. Neuropsychological tests that allow for comprehensive assessment of neural development from birth. Application of novel techniques in neonatal MRIs without anesthesia.
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Developing new imaging technologies for research and early diagnosis, including pioneering methods such as ultramicroscopy, new applications of dimensional analysis, and spectral resonance analysis. Identify new disease biomarkers (substances detected in blood or urine) that could be used both in the mother and the newborn.
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Lines research work
Consolidate and extend the pioneering experimental models to characterize the molecular mechanisms of diseases caused by prenatal programming anomalies. To investigate the molecular signaling pathways and new therapeutic targets revealed by cellular biochemistry.
Early identification is crucial to avoid future problems affecting the normal development of the child and thus reduce the impact that can produce both families and society in general
Microstructure and metabolomics
Brain connectivity
Diagnosis and therapy
Prematury
HEART
BRAIN
Clinic
Fetal cardiovascular programming
Image
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Platforms
Laboratory
Biobank
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cardiovascular fetal Programming
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Brain connectivity Leader: Elisenda Eixarch
Leader: FĂ tima Crispi The focus of this line of research is the prenatal problems that can cause an increased cardiovascular risk; among these problems are those derived from intrauterine growth restriction, pregnancies obtained after assisted reproduction techniques, prematurity, and others. The main objectives of the line include getting a better understanding of the pathophysiologic mechanisms of fetal cardiovascular programming, the development of biomarkers that allow early detection and monitoring of cardiovascular remodeling and finally to test therapies that can improve the cardiovascular prognosis of these children. To accomplish these objectives we integrate medical translational fetal medicine specialists, pediatricians and cardiologists, as well as biologists, biotechnologists and engineers.
The main highlights of this past year have been: Description and validation in fetal life of a new diagnostic method in functional echocardiography allow improved understanding of cardiovascular remodeling in fetal life. Development of a diagnostic algorithm that includes various cardiovascular parameters for
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the prediction of perinatal outcome in pregnancies with severe growth restriction. Promising preliminary results in various therapeutic strategies for the improvement of cardiovascular remodeling in prenatal life.
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Neurological Programming
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Leader: Magda Sanz About 10% of children have a neurodevelopmental problem throughout their lives. However, most of these problems are subtle and often, the imaging tests do not show any abnormalities. However, in most cases there has been an alteration in the maturation process of the brain that cannot be identified with the usual tests. For this reason, different research lines on brain development were created: Metabolomics and Microstructure: As part of our group’s overall goal of finding biomarkers and determining which children are at risk for anomalous neurodevelopment, we have developed a line of Metabolomics and Microstructure. In this line, doctors, biologists, psychologists, and engineers work together using different technologies, especially those based on MRI in order to find and define what the metabolic differences are in the brain of fetuses and children that are diagnosed with growth restriction and that can be found at risk for neurodevelopmental problems. Knowing what changes occur in the brain will be of great value in identifying and helping these children at risk, improving their prognosis.
The main objective of the connectomic research is to develop a quantitative imaging biomarker for early diagnosis of neurodevelopmental disorders. A new technology to measure brain function based on analyzing the connections in the brain by magnetic resonance imaging (MRI) is key in this research line. In which different techniques of MRI are being used, including diffusion MRI which provides information about the distribution of white matter tracts that connect different areas of the brain, functional MRI which provides information on areas of the brain that work together, and anatomical MRI which establishes the connection through morphological information of the different areas.
Diagnosis and Therapy in IUGR
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Leader: Francesc Figueras
The availability of these biomarkers would allow for early identification of neurodevelopmental disorders and, therefore, the implementation of specific programs of early stimulation and education to improve the development of these children.
This line of research aims at identifying before birth which babies with growth problems will have abnormal neurodevelopment. A majority of the babies considered small in utero are naturally smaller which does not entail any disadvantage for future development. However, a proportion of the small fetuses are due to problems of the placenta, which do not manifest themselves in any of the parameters that are commonly used in monitoring pregnancy. Our group was the first to observe that despite not being born prematurely, these babies have more neurobehavioral problems at birth that persist into childhood. When there are problems with the placenta, the fetus itself initiates a series of mechanisms to optimize the amount of available oxygen. One of the earliest mechanisms established is the redirection of more blood to the brain. Our group has developed a noninvasive method using Doppler quantification to measure how much blood reaches the brain. Babies who are born before this alteration have a slightly increased risk of neurodevelopmental problems. These subtle changes have been given more attention in recent years, and this attention will grow more if they are recognized as a family and social problem. The prenatal identification of at risk babies is especially important because preventive measures could be taken during pregnancy and childbirth, as well as during early childhood.
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PrEMATURIty
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Leader in specialized training center
Leader: Montse Palacio This line of research on prematurity aims to advance the knowledge of the causes of preterm birth. In recent years, despite improvements in managing a pregnancy, prematurity has not only remained common, but also has even increased in incidence. Since prematurity is the leading cause of perinatal morbidity and mortality, it is crucial to understand the determinants that trigger the premature delivery so that we can postpone the birth and improve perinatal outcomes, as well.
Given the high number of researchers who want to join our cutting edge research team, we are continuously searching for opportunities to receive financial backing from international institutions such as Marie Curie Research Network (European Union).
www.medicinafetalbarcelona.org/ docencia/es
With its long tradition of teaching, and of course its ties with the University of Barcelona, Hospital Clinic is an international leader in medical education. This allows our Research Team, with a large group of internationally renowned subspecialty training programs, to give students a high quality education of through both general training cycles and highly specialized courses, all with innovative
curricula, higher levels of interaction, and precise training objectives and deliverables. We receive financial backing from national societies (SESEGO) and international societies (Intl. Society of Ultrasound in Obstetrics & Gynecology and the Fetal Medicine Foundation), allowing trainees to obtain continuing education credits.
Being part of our research team is one of the most highly internationally sought after position in terms of training in Fetal and Perinatal Medicine; each year hundreds of applications are received for training in our center. During 2011 we selected 10 researchers with the best academic curricula. We have welcomed research staff such as:
Our research takes place in several areas: First, we are working to refine the detection of patients at real risk of preterm delivery, second, at the clinical level, we are working to optimize the management and care of neonatal patients, and finally we are developing noninvasive methods for monitoring lung maturity in fetuses. The development and improvements in each of these projects will allow us, firstly to have biomarkers to distinguish at risk patients from the patients who will follow a good evolution, thereby minimizing needless intervention and overtreatment, and streamlining the management of time and resources to achieve the best possible results.
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ANNUAL REPORT 2011
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Date: 16 de Mayo de 2011. Calification: Excelent Cum Laude por unanimidad. Director: E. Gratacós, F. Crispi Currently 10 researchers are preparing their doctoral theses in various international universities.
conferences and WORKSHOPS
We signed an agreement with the nongovernmental organization Action Aid Spain to develop a Latin American program of innovation, research, and training in the area of maternal and child health.
Some of our researchers have done stayed in other international centers in the context of different exchange programs. Here are some of their international projects:
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Salgrenska Hospital / Ostra (Goteborg, Sweden) specializing in intraamniotic inflammation. Dr. Teresa Cobo was there the last quarter of 2011, and many significant joint collaboration projects have resulted from her stay, as well as various articles in international journals. Yale University (New Haven, USA), Diagnostic Radiology Department/ MRI research center. Dr. Magda Sanz worked under the tutelage of Dr. Todd Constable, co-director of the research center, and Dr. Laura Ment, a professor of pediatric neurology at Yale University and a world-renowned expert in the study of the effects of prematurity on neurodevelopment.
Fetal and Perinatal Research Team
Karolinska University Hospital (Stockholm, Sweden) Neonatal Brain Imaging Group (NEOBIG). Currently Dr. Nelly Padilla is on a 12 months stay. This group is led by Dr. Ulrika Aden. Currently, Dr. Padilla is participating in a project related to brain damage and the neurodevelopmental abnormalities in extremely premature newborns. Katholieke University (Leuven, Belgium), Fetal Medicine Research Unit, led by Dr. Jan Deprest. Dr. Elisenda Eixarch has made a three-month stay led by Dr. Jan Deprest at this reference center of fetal therapy in Europe. Participation in a research project on fetal surgery resulted from her stay.
Doctoral thesis submitted in 2011 Elisenda Eixarch Roca. Universitat de Barcelona. Title: Brain reorganization in an experimental model of intrauterine growth restriction Date: 3 de Noviembre de 2011 Calificacion: Excelent Cum Laude por unanimidad. Director: E. Gratacós/F.Figueras Montse Comas Rovira. Universitat de Barcelona. Title: Cardiac Dysfunction by tissue doppler in early-and late-onset fetal growth restriction.
In 2011 the team participated in 19 scientific conferences of international scope and 15 of national scope; in total, we have presented over 35 oral presentations. 31st Annual Meeting Society of Maternal Fetal Medicine. 7-17 February. San Francisco (USA) IV Congreso de Atención Prenatal. 3-4 March. Gijón (España) 19º Congresso Portugues de Obstetricia e Ginecologia. 16-19 March. Porto (Portugal) 8th IEEE International Symposium on Biomedical Imaging (ISBI). 30 March- 2 Abril. Chicago (USA) 1st African Congress of Perinatal Madicine. 2-3 April. Addis Ababa (Ethiopia)
Congrès on Mortalité Maternelle et Néonatale. 5-6 May. Yoaundé (Cameroun) 9th Congress of the International Prenatal Screening Group (IPSG). 20-21 June. Barcelona (España) XI Congreso Colombiano en Medicina Perinatal . 15-18 June. Cali (Colombia) 10th World Congress in Fetal Medicine. 26 June. St. Julien.(Malta) 43rd European Brain and Behaviour Society Meeting, 9-12 September 2011 21st World Congress on Ultrasound in Obstetrics and Gynecology. 18-22 September. Los Angeles (USA) 10th World Congress of Perinatal Medicine, 3-6 October. Punta del Este (Uruguay) Advances in Fetal Imaging. The optimal combination of Fetal Technologies. Ultrasound meets MRI in the Louvre. 28-29 October. Paris (Francia) 6th World Congress on Tissue Banking, 9-11 November. Barcelona (España) EUROECHO, Fifteenth Annual Meeting of the European Association of Echocardiography 9 de December. Budapest (Hungría)
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ourstatistics 31/12/2011
50
10
124,14
36
publications during 2011
Total Impact Factor
Fellowships
Orals presentations in international conferences
119.726
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20
700
visits in our website to experience significant growth
attendances to conferences and workshops
publications IN SCIENTIFIC JOURNALS
The team has published 50 scientific articles featured in Placenta.
In 2011 the team published 50 scientific articles in 18 international journals. The Impact Factor of all of our publications is 124,14, according to the Institute for Scientific Information. 70% of the journals that have published our articles are in the first quartile,
and 100% are in the first decile. The article Impact on Cardiovascular Mortality and fetal Doppler of selective ligature of uteroplacental Vessels Compared with undernutrition in a rabbit model of intrauternine growth restriction earned the cover of the journal Placenta.
Poster presentation in internacional conferences
Diagnostic imaging tests for neurodevelopement in newly-born
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Ongoing Projects
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ANNUAL REPORT 2011
On November 30 Dr. Gratacos offered a lecture in Barcelona Cosmocaixa entitled: Fetal Programming - The medicine starts before birth.
Presence in the Media On 22 November the Research Team held in Barcelona CosmoCaixa the event “Hope for the problems of prenatal origin.”.
Dr. Eduard Gratacós in TEDxBarcelona a hope for the problems with prenatal origin This event, which stemmed from our desire to open our work and research to the society at large, had the aim of sharing the research advances developed in the maternal-fetal families, patients, associations, and professional balancing the expectations of our patients with competitive research. In the course of this event, each research line presented the most relevant projects that they were working on: “Quantitative imaging biomarkers, New methods based on connectomics for the prediction of abnormal neurodevelopment in children with fetal growth retardation”.
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“Fundació La Caixa” is funding this project. Children who suffered fetal growth retardation often have different brain development, which manifests itself through neurodevelopmental disorders and learning disabilities. This problem is “invisible” the first years of life, and when it becomes evident – usually at 6-7 years – it is difficult to solve. Early stimulation in the first years of life may improve and even prevent these problems in some cases, but it is necessary to demonstrate the differences in these abnormal and normal brains, to serve as biomarkers of abnormal development. Attendees to the event included 120 families accounting for a total of 50 children, in addition to nume-
Fetal and Perinatal Research Team
rous associations of patients and professionals. The event ended with a round table discussion: “Why is prenatal life key?”, Attended by Paula Adam, deputy director of the Research Information Agency, Evaluation, and Quality of Health of the Generalitat de Catalunya, Joan Bigorre, director of Innovation hospital Clinic, Carlos Manrubia, father of a patient, Jaime Montalvo, president of Action Aid-Spain and the aforementioned Dr. Gratacos. All participants supported research in the field of health, encouraging the creation of a critical mass of citizens, professionals, and politicians who are committed to the financing of such research.
news from the event: http://www.rtve.es/alacarta/videos/ telediario/reproducen-imagen-conexiones-neuronales-ninos-sufrenretraso-cognitivo-leve/1255475/ Presentation: Eduard Gratacós https://vimeo.com/42826342 Dafnis Batallé https://vimeo.com/42825530 Elisenda Eixarch https://vimeo.com/42838419 Magda Sanz https://vimeo.com/42837058 Testimony of a girl’s mother attended by the Team https://vimeo.com/43023037 A round table discussion https://vimeo.com/43020285 Màrius Serra https://vimeo.com/42822953
TEDxBarcelona Science is part of a program of local conferences put on independently, allowing you to enjoy an experience similar to TED conferences in different countries of the world. TED conferences are events where you see the most cutting-edge and innovative work in science and technology related to all fields with the aim of spreading interesting ideas. At the event Dr. Gratacos gave a speech and presentation on the current state of Fetal Medicine and the importance of research and development of new technologies to improve both the diagnosis and therapy options available.
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we have been in the news
http://www.elpuntavui.cat/noticia/ article/2-societat/14-salut/478462. html
Journey into a brain of 20 weeks of gestation http://www.saludymedicina.org/ tecnologia/cerebro-de-20-semanasde-gestacin
PSYCHOLOGIES: The future is in the uterus. http://medicinafetalbarcelona.org/ investigacion/documents/psychologies.pdf
Spain, a world leader in the early diagnosis of brain damage in children. http://www.cope.es/sociedad/2211-11--espana-pionera-mundialen-el-diagnostico-precoz-de-danocerebral-en-ninos-267344-1
The Clinic detects the risk of school failure from the first years of life. http://www.lavanguardia.com/ vida/20111123/54239211423/clinicdetecta-riesgo-fracaso-escolarprimeros-dias-vida.html
A Spanish team, pioneers in the early diagnosis of brain damage in children http://sociedad.elpais.com/ sociedad/2011/11/22/actualidad/1321916406_850215.html
The Clinic detects the risk of school failure from the first years of life http://medicinafetalbarcelona.org/ investigacion/documents/prensa/ LAB-DrGratacos.pdf
Identified the first biomarker for early diagnosis of brain damage in children. http://www.abc.es/salud/noticias/ identifican-primeros-biomarcadores-para-diagnostico-10671.html
“More fetal is less fatal� http://www.lavanguardia.com/opinion/articulos/20111124 /54238504756/marius-serra-masfetal-menos-fatal.html
The brain damage in premature infants was detected before the year of life. http://www.larazon.es/noticia/501el-clinic-logra-los-primeros-biomarcadores-para-el-diagnostico-precozde-dano-cerebral-en-ninos
Saved before birth http://hemeroteca.lavanguardia.com/preview/2011/07/29/ pagina-20/87262993/pdf.html? search=salvado antes de nacer Reproduce the image of the neural connections of children who suffer a mild cognitive delay http://www.rtve.es/alacarta/videos/ telediario/reproducen-imagen-conexiones-neuronales-ninos-sufrenretraso-cognitivo-leve/1255475/
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Clinic researchers discover biomarkers for early diagnosis of brain damage. http://www.324.cat/noticia/147 4932/societat/Investigadors-del-Clinic-descobreixen-els-biomarcadorsper-al-diagnostic-precoc-del-danycerebral The Clinic devises a technique that can detect brain damage in babies
Fetal and Perinatal Research Team
Doctors of gestational life. http://www.medicinafetalbarcelona. org/investigacion/documents/prensa/el_periodico_01_02_2011_1.pdf http://www.medicinafetalbarcelona. org/investigacion/documents/prensa/el_periodico_01_02_2011_2.pdf The text Eduard Gratacos: Spain has published very good ideas without setting up patents. Business Dossier 8 to 14 July 2011. Dr. Eduard Gratacos is one of the most recognized figures in neonatal medicine in our country. In addition to the position he holds in the Clinic of Barcelona, he is also director of the Research Group in Fetal and Perinatal Medicine, a position from which he makes a review of the current situation of research in our country, and proposes a new formula that is modern, innovative, and based on agile and independent structures and a necessary human capital base. Fetal therapy, Radio interview with Eduard Gratacos. (http://www.rtve.es/alacarta/audios/ tinc-un-pla-secret/tinc-pla-secret-entrevista-eduard-gratacos/1202435/)
119.726 visits in our web
Also Follow Us:
our web www.medicinafetalbarcelona.org received in 2011 a total of 119.726 visitors, experienced significant growth during the last quarter of the year. 60% were new visitors. 59% of visits were from places in Spain, although the site has been visited from over 100 countries worldwide. Our site has been recognized with an award as being one of the highest quality medical websites. (Certificate of Health and Hon Web Interest Code, and accredited by the Web Medical College of Barcelona Metges). To stay closer to our website users, we created a Facebook profile as well as video channels on Youtube and Vimeo.
Fetal and Perinatal Research Team
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ANNUAL REPORT 2011
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ACKNOWLEDGEMENTS SPONSORS WHO HELP US REALIZE SCIENTIFIC ADVANCES
collaborations Our objective of establishing a large research center of reference in Europe, focusing on prenatal pathology and specialized in fetal brain and heart, can only be achieved through joint projects with other leading hospitals and universities in research.
ESPAÑA
· Universidad de Jaén San Francisco · Instituto de Investiga- · Alpert Medical School
· Universitat de Barcelona of Brown University, ción en Bioingeniería · Hospital de la Santa de la Universidad de Providence · Children’s Hospital of Creu i Sant Pau Zaragoza · Fundación · Institut Català Philadelphia, Philade Ciencies delphia Jimenez Díaz · Hadassah-Hebrew Cardiovasculars · Parc Científic University Medical INTERde Barcelona Jerusalem NATIONAL Centers, · Universitat Tel Aviv University · Consorcio Eurofoetus · Edith Wolfson MediPompeu Fabra · Universidad University Hospitals cal Center · Consejo Nacional de Leuven, Bélgica Politécnica de · Cerebra Foundation Ciencia y Tecnología Cataluña · ICFO, Instituto de for the Brain (CONACyT) · Transmural Biotech Injured Child, Wales Ciencias Fotónicas · King’s College · Universidad de (Spin-off) · Hospital, London Santiago · Hospital Necker de Compostela · Enfants Malades, · Universidad companieS Paris de Navarra · University of Lund · SIEMENS · Centro de · KARL STORZ Investigación Príncipe Thrasher Research · Rusell & Reynolds Fund, Salt Lake City Felipe, Valencia · BioTalentum · Universidad Pablo de · University · CIBER-ER of California, Olavide, Sevilla
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Fetal and Perinatal Research Team
Also, our mission would not be possible without funding that supports our competitive and innovative research. Our research group has received numerous grants from public and private entities, as well as from individuals, which have allowed us to make significant scientific advances. Collaborations North America
Reference research center in southern Europe,
Collaborations south america
The support and commitment of all who believe in our work contributes very effectively to a hopeful future for those affected, their families, and ultimately the entirety society.
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www.medicinafetalbarcelona.org Sabino de Arana, 1 路 o8o28 Barcelona Tel. +34 93 227 99 31 路 Fax + 34 93 227 56 05 managem@hospitalclinic.org