The research within our LUMC departments is conducted within departmental research programmes. The research programme below is embedded within the department of Obstetrics.
- Research programme: Research into fetal development and medicine
- Department: Obstetrics
- Programme leader: Prof. Dr. J.M.M. van Lith
- Principal investigators: Prof. Dr. D. Oepkes, Dr M. Haak, Dr T. van de Akker, Dr M.L. van der Hoorn
- Biomedical research profile: Immunity, Infection and Tolerance
- Generic research profile: Innovation in Health Strategy and Quality of Care, Ageing
Aim and focus
The goal of obstetrics is to provide the best care for pregnant women, aiming for happy mothers and healthy babies. Leading causes of fetal and neonatal morbidity and mortality are preterm birth, fetal growth restriction and congenital anomalies. Major causes of maternal morbidity are postpartum haemorrhage and pre-eclampsia. An increasing challenge is posed by pregnancies in women with obesity and other morbid conditions. In fact, pregnancy outcomes are impacted directly by population health, and healthy ageing starts with a healthy pregnancy.
The program focuses on 3 themes:
- fetal medicine
- maternal health
- reproductive immunology
The fetal medicine theme focuses on fetal therapy and fetal cardiology. The fetal therapy research group is led by Dick Oepkes, professor in Fetal Therapy. The Leiden research activities in this relatively new field of medicine combines development of innovative diagnostic and therapeutic modalities (e.g. with TU Delft and ErasmusMC in Medical Delta) with clinical studies including randomised trials to evaluate our care. Given the rarity of the diseases, most research activities encompass (international) collaboration (see below). Our research is closely integrated with the division of Neonatology, led by Professor Enrico Lopriore, with whom we have established an internationally highly esteemed program for long-term follow-up of children born after fetal therapy.
The fetal cardiology research group is led by Monique Haak. Cardiac malformations are the leading cause of death in the first year of life in term born children. The research of this group focuses on understanding (ab)normal cardiac development and the neurological development in these fetuses, the use of innovative (ultrasound) techniques to monitor cardiac development and long-term follow-up from a fetal perspective. The group works in collaboration with the fetal medicine groups of the AMC and VUMC, the departments of pediatric cardiology (prof Nico Blom) and the department of Anatomy (Monique Jongbloed).
Our department has traditionally contributed to research into maternal morbidity and mortality, through the LEMMoN-studies and by helping to establish both the Netherlands Obstetric Survey System (NethOSS), as well as the International Obstetric Survey System (INOSS). Research within this field is now led by Thomas van den Akker, who spent part of his fellowship perinatology at the University of Oxford. A collaboration has been initiated with the National Perinatal Epidemiology Unit at Oxford, a world-leading unit in maternal health research. Aim is to increase research activities in this field regionally (Leiden-The Hague), nationally (through NethOSS and the national maternal mortality review committee of which Thomas is a member) and internationally (through the collaboration with Oxford and INOSS). This promising field of research has clear links with the new strategic focus on population health, and collaboration is sought with other departments in our centre, such as the departments of clinical epidemiology, public health and cardiology.
Our basic science research focuses on maternal immunological adaptations of pregnancy. In a normal pregnancy, immunological regulatory mechanisms result in the maternal acceptance of the partial allogeneic fetus. We study the immunological interaction at the maternal-fetal interface in uncomplicated pregnancies, in oocyte donation pregnancies and in pregnancies complicated by recurrent miscarriages and relate these findings to clinical care. Marie-Louise van der Hoorn is leading this research theme.
Position in international context
Our country is unique in having, since 1965, one national centre for invasive fetal therapy, the LUMC, one of the largest fetal treatment centres in the world. We are initiators and active participants in international networks, such as the International Fetal Cardiac Intervention Registry (www.ifcir.org ), and the Horizon 2020-funded BOOSTB4 consortium (www.boostb4.eu) Our department has a close research collaboration with the University of Toronto, University Hospital Gasthuisberg in Leuven, the Karolinska Institute in Stockholm and the University of Texas in Houston.
The PRECOR registry of the LUMC one of world’s largest registry of cases (>3000) with congenital heart defects, registered already in fetal life. This registry is able to compare cases that were detected in prenatal screening programs, to those who weren’t. Furthermore follow-up studies from fetal life onwards hardly exist.
Aforementioned collaboration with the University of Oxford has been initiated, and we play an active rol in INOSS, in which research groups from the United Kingdom, Germany, Belgium (Universities of Leuven and Ghent), France (INSERM, Paris), Italy, Spain, Denmark, Sweden, Norway, Finland, Australia and New Zealand are included. One of the aims of the collaboration with Oxford is to expand succesful maternal health interventions, such as confidential enquiries into maternal deaths, to the global level.
Our research is internationally well known and cited. Already in the past and currently we have several collaborations with laboratories abroad (e.g.Karolinska, AC Staff for acute artherosis, Boston, Karumanchi for preeclampsia studies, DW Bianchi for oocyte donation pregnancies)..
Content / highlights / achievementsFetal medicine
- Leading international centre for management of red cell alloimmunisation (Rhesus-disease) and alloimmune thrombocytopenia (FNAIT) in pregnancy, research with Sanquin Amsterdam/LUMC (Prof. Masja de Haas), numerous grants (>2M euro), publications in top-journals NEJM, Blood, >10 PhD theses.
- Leading international centre for laser therapy of twin-to-twin transfusion syndrome (TTTS) and other monochorionic twin complications. International multicenter RCTs, first description of ‘new’ disease (TAPS), highly cited publications (Lancet) Initiator and coordinator of the Int. Fetal Cardiac Intervention Registry, with 26 member-centres worldwide. Top-publications (Circulation), >10 PhD theses.
- Technical innovations within Medical Delta collaboration (Prof. Jenny Dankelman) e.g. 3D printing to treat fetal spina bifida, First prize Best Tech Idea 2016, for 3D printing for fetal spina bifida, KIJK Magazine, The Netherlands , First prize Open Mind Competition 2015, for World Without Wheelchairs project, STW, Delft. Coverage in national newspapers and prime-time TV news.
- EU-funded Horizon 2020 study on fetal mesenchymal stemcell treatment for fetuses with osteogenesis imperfecta (with Karolinska Institute Stockholm)
- The largest registry of fetal cardiac cases (2 PhD theses)
- 2017: launch of fetalheartacademy.nl which is an image databank for fetal medicine specialists, free accessible
- Funded collaboration with Toshiba MEdical Systems to explore innovative ultrasound techniques.
- Collaboration with the NPEU, Oxford, established (2017)
- First international studies with INOSS-consortium completed (2016, 2017)
- Contribution to definitions for maternal morbidity and maternal near miss with the World Health Organization and INOSS (2014-2017)
- Transfusion studies in women during major obstetric haemorrhage studies (TeMpOH-studies): first papers published, four PhD projects in varying stages (2017)
- Ongoing studies to maternal mortality at national level (1 PhD) (2017)
- Exploration for research collaboration with departments of clinical epidemiology, public health and others (current)
- Immunology in recurrent miscarriage and oocyte donation pregnancies: study T cell populations, macrophages, seminal fluid, HLA-G and relate the outcomes tot clinical characteristics. 3 PhDs completed, 4 ongoing.
- Long-term outcomes of oocyte donation pregnancy.
- Role of endothelial dysfunction in preeclampsia
- Optimizing new laboratory techniques in placental immunology (Cytof)
- Oocyte donation pregnancies have more complications (2009)
- More HLA antibodies and more activated T cells in oocyte donation pregnancies (2014, 2013), related with the number of HLA mismatches (2013)
- Loss of placental thrombomodulin in oocyte donation pregnancies (2016)
- Definition of Massive chronic intervillositis (2017)
Future themesFetal medicine
- Translational research in alloimmunisation (red cells and platelets), with Sanquin and international partners (expecting ground-breaking studies in next 5 yrs)
- Medical Delta main theme next 5 years via founding of Fetal & Neonatal Care Institute, developing innovations e.g. sensortechnology, non-invasive treatment options (HIFU), e/ and m/health, big data analysis, home monitoring, with private partners/industry.
- Long term follow-up studies on all children treated as fetuses, and their mothers.
- Stem-cell and gene therapy for fetal diseases
- Long term follow up studies in CHD. Neurological protection programs for fetuses with CHD. The development of prediction models to predict left hypoplastic heart syndrome or borderline left ventricle.
- Projects to identify neonates that need immediate treatment after birth and those who are save to stay with the mother for hours.
- Translational research to understand abnormal development and to intervene with those who worsen.
- Maternal health research, with a strong population health component at regional (Leiden – The Hague), national and international levels.
- Long term follow up studies
- Introduction and research of ICHOM
- Expanding the cooperation with Oxford, NPEU
- Expanding translational research, focussed on hemorrhage and nephrology/pre-eclampsia
- Translational research: To relate the findings of basal immunological sciences in the clinics. Find the best (antenatal) care for oocyte donation pregnancies based on the knowledge gained from laboratory studies. Perform a randomized controlled trial in patients with recurrent miscarriages based on the findings of the immunological studies.
Cohesion within LUMCFetal therapy
Our research is done in close collaboration with Sanquin/Clinical Epidemiology LUMC (Prof De Haas, Prof Van der Bom), division of Neonatology (Prof Lopriore, Dr. Te Pas), Immunohematology (Prof Fibbe, Prof Zwaginga and Prof Lankester), and Pediatric Cardiology (Prof Blom).
This research is performed in close collaboration with Cardiology (Dr. Kies, Dr. Jongbloed, Prof Schalij), Clinical Epidemiology (Prof Van der Bom), and Public Health (Prof Reis), Sanquin/Clinical Epidemiology LUMC (Prof De Haas, Prof Van der Bom), Nephrology (Prof Rabelink, Dr Teng).
Reproductive immunologyThis research is performed in close collaboration with the departments of Immunohematology and Blood transfusion (Prof Claas, Dr Heidt and Dr Eikmans), Pathology (Prof Bruin, Dr H. Baelde), Nephrology (Prof Van Kooten) and Gynaecology (Dr Louwe and Dr Lashley).