Child research

ChiLD 

research

Colophon 

Child Health magazine, edition 2019 

Publisher 

This magazine is published by UMC Utrecht, 

Strategic Program Child Health 

Editors 

Celine Uit de Weerd-Bakker, Anneke van der Brug 

Magazine concept, design and art direction 

UMC Utrecht Design & productions; 

Barbara Hagoort, Laura Langenbach 

Contributors 

Kors van der Ent, Anneke van der Brug, Berent Prakken, 

Mireille Bekker, Kitty Bloemenkamp, Jeroen Dudink, 

Floris Groenendaal, Manon Benders, Helen Torrance, 

Frank Broekmans, Gijs van Haaften, Hans Kristian Ploos 

van Amstel, Albertien van Eerde, Marc Lilien, Hans Breur, 

Peter van Tintelen, Sabine Fuchs, Peter van Hasselt, 

Judith Jans, Nanda Verhoeven, Jeffrey Beekman, 

Saskia van Mil, Bas Vastert, Jorg van Loosdregt, 

Femke van Wijk, Louis Bont, Patricia Bruijning, 

Marry van den Heuvel-Eibrink, Roelie Wösten-van Asperen, 

Hanneke van Santen, Jaap van Laar, Nico Wulffraat, 

Harry Heijerman, Kathelijn Fisscher, Roger Schutgens, 

Elise van de Putte, Tim Takken, Janjaap van der Net, 

Marianne Boes, Marjolijn Ketelaar, Sanne Nijhof, 

Martha Grootenhuis, René Eijkemans, Niels Eijkelkamp, 

Freek Hoebeek, Joost Frenkel, Cyrus Park. 

colofon 

Copy editors 

Sarah Opitz, Cyrus Park 

Coordination photography 

UMC Utrecht Design & Productions; Jelle Westerhoff 

Photography / contributing photographers 

UMC Utrecht Design & Productions; 

Rudi Hovig, Ed van Rijswijk, Thomas Dobber, Ivar Pel 

Getty Images, Unsplash 

Illustrations 

Barbara Hagoort, Laura Langenbach 

Print 

Revon 

Contact 

Anneke van der Brug 

Program manager Child Health 

abrug@umcutrecht.nl 

0031 6 16 36 11 51 

www.umcutrecht.nl/childhealth 

childhealth@umcutrecht.nl 

2 UMC Utrecht - Child research 

The photographs on the 

coverpage and this page 

show microscopic pictures 

of intestinal organoids used 

by several research groups 

of the Child Health Program

UMC UTRECHT I WILHELMINA CHILDREN’S HOSPITAL 

 

Child Health 

in Utrecht 

 

In the 17th and 18th centuries, medical care for children was in the hands of general 

physicians and surgeons. It was not until the second half of the 19th century that 

doctors began to focus on caring for sick children and formed the basis for current 

pediatric medicine. 

The Wilhelmina Children’s Hospital was founded in 1888 and 

is one of the oldest children’s hospitals in the world. From the 

very beginning, excellent medical care and new medical 

developments went hand-in-hand, working closely with the 

Utrecht University. In 1997, the children’s hospital merged 

with the Academic Hospital Utrecht and the medical faculty 

of Utrecht University to form the University Medical Center 

Utrecht (UMC Utrecht). 

Today, the UMC Utrecht is one of the largest academic 

centers in the Netherlands. Patient care and biomedical 

research are closely linked, which creates an environment 

where scientific advancements quickly move from bench to 

bedside. The UMC Utrecht finds itself in the middle of a 

vibrant biomedical research community: Utrecht Life 

Sciences. This represents a strategic alliance in education, 

research and entrepreneurship in the domain of the life 

sciences in the Utrecht area, located in the very heart of 

the Netherlands. 

The UMC Utrecht’s strategy ‘Connecting U’ concentrates 

research into six programs, each with a focused number of 

disease targets and patient care is integrated into these 

programs. Care and research for sick children are still at the 

heart of the organization, and one of the six research 

programs is ‘Child Health’. This Program is an integrated 

framework for child-centered interdisciplinary research, 

aligning patients, clinicians, investigators and resources, so 

that it can lead by filling significant gaps to improve the lives 

of children during childhood and thereafter. 

This magazine gives you an insight into the program and 

introduces you to our researchers and their subjects. 

We invite you to contact them and work together - 

because children are our future! 

I believe the children are our 

 

future 

Teach them well and let them lead the way 

Show them all the beauty they possess inside 

Give them a sense of pride to make it easier. 

- Whitney Houston, 1985 

Kors van der Ent Chair of Child Health 

Program UMC Utrecht. 

Care for chronic diseases in the future 

asks for rigorous changes in our 

old-fashioned health care systems. 

- Kors van der Ent 

UMC Utrecht - Child research 3

06Contents 

The Child Health Program 

Ante- and 

perinatal 

damage 

Congenital 

and hereditary 

disorders 

Severe 

inflammatory 

disorders 

Postoncology 

When you 

save the 

mother, 

you save 

the family. 

- Kitty Bloemenkamp 

Your DNA 

at the 

center 

of care. 

- Hans Kristian and 

Ploos van Amstel 

Prevention is 

better than 

treatment. 

- Patricia Bruijning 

 

Our mission in 

pediatric oncology 

research is to 

improve cure rates 

for all children and 

to enhance quality 

of survival. 

- Marry van den Heuvel-Eibrink 

10 16 22 

30 

32 

Strategic Themes 

40 Unique Resources 

32 

36 

38 

Lifecycle 

Interdisciplinarity 

Mental & Physical Health 

40 Patients cohorts 

41 

45 

Facilities & Expert Knowledge 

Clinical Trials 

46 Education and Talent 

4 UMC Utrecht - Child research

CHILD HEALTH PROGRAM UMC UTRECHT 

Collaborations 

& networks 

Visualization network of collaboration partners of Child Health - based 

on co-authorship of 1324 articles and reviews in Web of Science 

published in 2016-2018. The graph shows the 100 organizations that 

Child Health most frequently collaborates with. Bubble size is 

proportional to number of publications, line thickness to the number 

of papers co-authored by researchers from the respective organizations. 

connections are only shown between organizations that co-published 

10 or more papers. 


The Child Health Program 

of the UMC Utrecht 

UMC Utrecht is one of the top-ranked academic medical centers 

in Europe in which patient care and biomedical research are 

closely linked. Partners, for example the Hubrecht Institute, can 

be found at a close distance, and collaboration with the Faculties 

of Veterinary Medicine and Science at Utrecht University 

reinforces the relationship between animal and human health 

and the environment. The UMC Utrecht has been awarded 

international accreditation on quality of care, research and 

education by the Joint Commission International (JCI). 

Our program, Child Health, is one of six 

hospital-wide strategic research programs. 

The diseases we focus on are characterized 

by their influence on an individual’s entire 

lifespan as they often start at the 

beginning of life, or even before birth, and 

can have consequences far into adulthood. 

Within our Child Health program, we 

ensure that our ‘Cycle of Life’ approach is 

strongly intertwined with innovation. 

Goals 

We focus on healthy development of a 

child, from pre-conception to adulthood. 

We’ve established an interdisciplinary 

child-centered research community that 

aligns with the European Commission’s 

philosophy of Responsible Research and 

Innovation (RRI) and aims to: 

Anneke van der Brug, MSc is the Child Health Program 

manager. She enjoys stimulating (clinical) researchers working 

together in multidisciplinary research and is eager to continuously 

think up opportunities to promote excellent scientific results. 

abrug@umcutrecht.nl 

Kors van der Ent, MD PhD is chair of the Child Health 

Program. He is an experienced pediatric pulmonologist with 

special interest for chronic diseases, like cystic fibrosis. Besides 

top-notch science he is mainly focused on what really matters for 

patients and their families. 

cent@umcutrecht.nl 

• Improve pediatric disease outcomes 

within a lifespan context. 

• Cure congenital and hereditary diseases 

by unravelling pathogenesis; by developing 

diagnostic and prognostic markers 

and tools; and by developing and implementing 

novel therapeutics and lifestyle 

interventions. 

• Improve resilience and quality of life for 

children and their relatives during childhood 

and thereafter. 



By collaborating 

we can multiply 

our 

 

success. 

- Anneke van der Brug 

Societal impact 

In the past few decades, the field of 

pediatrics has been successful in 

combating disease and the life expectancy 

of many disorders has significantly 

improved. Unfortunately, although children 

may survive their disease, they’re 

burdened with long-term physical and 

mental consequences. This requires drastic 

changes for future healthcare: Pediatrics 

should focus on the development of children 

towards healthy and balanced adults. 

Our Child Health Program is dedicated to 

developing disease prevention strategies, 

as well as safe treatment options for 

children, which requires intensive 

collaboration and cross-fertilization 

between our basic and clinical scientists. 

But most importantly, our program is 

constantly interacting with children 

themselves and with the environment in 

which they grow up, including their family, 

school, sports clubs and broader living 

environment. Our program is an active 

participant in the midst of a child’s society. 

 

Research 

Areas 

The Child Health Program of the University 

Medical Center links top referent care for 

pediatric patient groups to interdisciplinary 

research. This ranges from fundamental to 

translational to longitudinal applied medical 

research. All chronic diseases within the focus of 

our program are similar in that they emerge 

early, in the beginning of life and can have 

consequences far into adulthood. Our research 

areas high lighted in this magazine are: 

Ante- and perinatal damage 

This program has a life-cycle character hosting several 

Centers of Excellence. It provides high quality care and 

research through the periconceptional, antenatal and 

perinatal phases up to neonatal intensive care, aiming for 

the best long-term outcome of child health. Women, 

babies and their families are the center of our service as 

we strive for excellence and innovation. 

Congenital and hereditary disorders 

Many disorders of genetic origin are rare and require 

academic specialist care. The Child Health Program 

focuses in particular on congenital diseases of the heart, 

liver and kidney and plays a key role in respective 

European Reference Networks. 

Severe inflammatory disorders 

We host several Centers of Excellence for children with 

sustained severe inflammatory disorders, such as Juvenile 

Idiopathic Arthritis, Cystic Fibrosis, Inflammatory Bowel 

Disease and Recurrent Respiratory Tract Infections. 

Post-oncology 

Treatment of cancer in children can result in severe 

physical and psychosocial consequences later in life. The 

Child Health Program closely collaborates with the 

Princes Máxima Center to improve long term outcomes of 

cancer treatment. 

Let’s collaborate on a culture 

of trust and innovation. 

- Kors van der Ent 


Berent Prakken, 

Acting Dean: 

}What I most appreciate about 

the Child Health program is that 

it thrives to deliver top notch 

science and translate it into 

societal impact.~ 

Partnering with society 

Today, scientific discovery and societal needs 

go hand-in-hand. One does not preclude the 

other. Because of this, there’s a great deal of 

cooperation between the Child Health Program 

with external social partners such as the 

municipality of Utrecht, the Trimbos Institute 

for Mental Health, the Jantje Beton Charity and 

a large number of patient organizations. 

Together, we ensure that basic science and 

clinical science harmonize to revolutionize 

patient care, and we’re motivated by both 

acquiring and applying knowledge. 

Team sport 

There’s a reason why we do what we do. We’re 

curious, we’re motivated, we’re passionate. We 

push our research beyond conventional 

questions. If we discover an important new 

gene, we don’t stop with a beautiful genetics 

paper. Instead, we continue hunting for the 

protein it encodes, and for its function. This 

feeds our passion for healing patients and we 

cannot do this alone. Fortunately, we don’t have 

to. From the molecular biologist discovering a 

molecule to the translational scientist 

investigating methods of delivery, to the 

physician making a diagnosis, to the 

psychologist encouraging adherence, to a 

treatment regimen, to the patient foundation 

focused on patient experiences. We’re all in this 

together. It’s no longer just a handful of 

researchers, but really a team sport. 

Berent Prakken 

Professor , Pediatric Immunology, Acting Dean, 

Education, Director, Biomedical Education Center 

3 Strategic Themes 

The research areas within the Child Health 

Program are cross-linked by three Strategic 

Themes that are represented in all research areas. 

1. Life-cycle research 

Prognosis of pediatric diseases have improved dramatically 

over the past few decades. For example, the life expectancy 

of children with cystic fibrosis has increased from about 10 

years in the 1950s to almost 50 years in current times. The 

first heart surgery in children was performed in at the end 

of the 1940s, when the lifespan was very short. Today, heart 

surgery is routine and most children with congenital heart 

disease are operated on and therefore have a normal life 

expectancy. Advances in cancer research and care are also 

providing a better and longer quality of life for children 

with cancer. 

The advancements in survival rates and success of 

combating acute complications have, in turn, changed care 

requirements of pediatric patients. New long-term 

complications of diseases are emerging, for example, 

cardiac arrhythmias can develop in adults after pediatric 

heart surgery and 40% of children with cystic fibrosis 

develop diabetes in adulthood. In addition, the effects of 

drug treatment in children with, for example, juvenile 

rheumatoid arthritis on the function of the liver, kidneys 

and lungs in adulthood are unknown. Research in 

chronically ill children demands parallel focus on longterm 

health for adults. 

bprakken@umcutrecht.nl 



2. Interdisciplinary innovation loops 

Our Child Health Program has created a scientific infrastructure 

that integrates various fields of biomedical research connected 

to groups of children with chronic diseases and their parents/ 

relatives. Advancing research for the benefit of these children 

requires an interdisciplinary approach including basic, 

translational and applied medical research. 

Patient problems, new technologies and societal developments 

continuously raise new research questions. Our 

coherent, interdisciplinary research strategy enables us to 

answer these research questions and discover meaningful 

outcomes for patients, their families and society. Therefore, all 

of our scientists and professionals who are involved in the care 

of our sick children, collaborate closely and share the same 

ambition to find the best solutions for our young patients. In 

addition, we’re dedicated to communicating our findings to 

our patients, relatives and the public; there is clear value in 

collecting feedback and properly evaluating our research as 

these will inevitably lead to new research questions. It is 

through this innovation loop that societal issues are considered 

when defining research directions, and where we can 

accelerate scientific results quickly from bench to bedside. 

I am daily impressed 

 

by 

the talent of the people 

who already work and 

study at these 

organizations. We must 

ensure that they can 

thrive and contribute to 

solving the social 

problems that our 

world faces. 

- Professor Anton Pijpers, 

President Utrecht University 

3. Physical – mental interaction 

Physical restrictions in childhood can have profound 

influence on the psychosocial development and identity 

formation in adulthood. Pain and discomfort in early life 

can affect basic trust in children. Deprivation from 

parents, families and friends during early life might 

influence social adaptations. Absence from school and 

inability to participate in sports might have a negative 

impact on the development of resilience in adolescence. 

It’s not enough to only pay attention to the physical 

health of children. On the other hand, psychological 

problems during childhood can have major adverse 

effects on medical treatment and the course of a disease. 

For example, denial of symptoms and poor adherence to 

therapy can highly influence outcome of chronic diseases. 

Therefore, we pay particular attention to the development 

of children with chronic diseases and study determinants 

of, for example, pain and fatigue at both the basic science 

and clinical care levels. This can help to develop and 

evaluate intervention programs. Our ultimate goal in this 

strategic theme is to empower and to engage children 

and their relatives to be fit for their future. 

Health and happiness are broad concepts. Chronically 

ill children indicate that they feel happy too though 

they are ill. By support from the environment and the feeling 

just to be able to participate, at school and at 

 

home. 

- Jan van Zanen, mayor of Utrecht 


ANTE- AND PERINATAL DAMAGE 

Reproductive care 

before, during and after birth 

kbloemen@umcutrecht.nl mbekker3@umcutrecht.nl 

Mireille Bekker, MD, PhD 

is a maternal fetal medicine 

specialist with an interest in 

fetal medicine, counseling, 

patient empowerment and 

eHealth in obstetric care. She’s 

a member of the board of the 

national NIPT consortium that 

performs nationwide implementation 

studies (Trials by 

Dutch laboratories for 

Evaluation of Non-Invasive 

Prenatal Testing). Mireille is the 

project leader of several 

research projects regarding 

home telemonitoring and 

other eHealth strategies in 

obstetric health care. 

Kitty Bloemenkamp. MD, 

PhD is and has been a PI of 

several randomized controlled 

trials, observational studies 

and experimental studies in 

the field of maternal health. 

She is the Chairman of Nethoss 

(Netherlands Obstetric Survey 

Study), National Enquiry of 

Maternal Death Review, 

Netherlands and of INOSS 

(International Network of 

Obstetric Survey Systems). 

Improving the health of women and 

children is a global public health issue. 

This mission was adopted by all United 

Nations Member States in 2015 and 

addresses sustainable development to 

ensure healthy lives and promote wellbeing 

at all ages. 

In this research area of Child Health, we focus on reproductive, 

maternal, newborn and child health. More specifically, we develop 

novel clinical strategies to innovate and improve the quality of care for 

the mother, fetus and child by integrating research with clinical care. 

This includes translational research, advanced imaging technologies, 

creating and integrating patient registries, diagnosis accompanied by 

genetic testing, eHealth, auditing to evaluate impact and value-based 

health care approaches. This is done in close collaboration with our 

colleagues in the fields of fertility, gynaecology and neonatology. 

In this way we investigate the entire lifecycle from preconception and 

complicated pregnancy to delivery, postpartum and consequences of 

these complications later in life. 

eHealth and high-risk pregnancy 

eHealth converges healthcare and technology, and is allowing our 

patients to actively participate in their own healthcare regimens. It also 

provides our physicians up-to-date information about our patients, in 

real-time, making diagnosis and treatment more efficient and 

accurate. And with the availability of mobile phones and internetbased 

applications, we can reach women and their babies in 

improverished areas. 

We often use eHealth methods in our research and care, and to share 

our findings. For example, women with high-risk pregnancies need to 

visit the hospital frequently, which may become burdensome on both 

the mother and unborn child. We’re currently running two studies, 

Safe@home and HOTEL, using smart telemonitoring systems. In the 

SAFE@home study, we monitor pregnant women at home for high-risk 

factors, for example high blood pressure and diabetes, reducing the 

number of visits they need to make to the doctor. In the HOTEL study, 

the fetal condition is monitored at home by a fetal cardiotocography 

device instead of hospital admission or daily visits. 



Life 

starts 

in the 

uterus. 

- Mireille Bekker 

 

Empowering women and their doctors 

Through previous eHealth studies on maternal health, we’ve 

discovered a need for reliable registration methods and audit 

processes for maternal and neonatal mortality. In addition, morbidity 

must be recorded in order to assess strategies on improving health 

conditions for women and their babies. Our goal is to translate our 

findings, as well as eHealth technologies, to help women, and their 

doctors monitor their pregnancies outside of the hospital in low to 

middle income countries. We aim to improve the quality of care for 

women and their families, and empower them through novel 

healthcare systems. 

 

When you save 

the mother, you 

save the family. 

- Kitty Bloemenkamp 


Building better brains 

Improvements in fetal and neonatal care 

have significantly reduced mortality in 

preterm infants and critically ill term infants. 

Unfortunately, half of the infants admitted to 

the neonatal intensive care unit (NICU) 

experience long-term neurodevelopmental 

problems, including cognitive deficits, motor 

disabilities and psychiatric diseases. This 

creates a lifelong burden, both socially and 

financially, for the affected individuals and 

their families. 

We’re on a mission to “build better brains” 

for vulnerable infants. Adverse early life events 

such as preterm birth, neonatal cardiac and 

non-cardiac surgery and hypoxic-ischemic 

encephalopathy can have a profound effect on 

brain development. Our neonatal neurology 

research group studies these events in relation to 

the developing infant brain by combining 

routine clinical neuroimaging (ultrasound and 

MRI), neuromonitoring (aEEG and NIRS) and 

neurodevelopmental follow-up. 

Babies get stressed too 

Premature infants are suddenly thrust into the 

bleak and sterile environment of the NICU and 

expected to thrive. During this period, exposure 

to stressful stimuli causes significant 

neurobiological changes affecting brain volume, 

DNA methylation and the hypothalamicpituitary-adrenal-axis. 

We’re investigating the 

effects of early stress on brain development and 

are optimizing neonatal care by enriching the 

extra-uterine environment and increasing 

parental involvement. Together with our national 

(Hippo-trial) and international research partners 

(University of Leuven, Kings College London, 

SickKids Toronto), we’re investigating how stress, 

such as painful procedures, and stress relievers, 

such as skin-to-skin care and sleep, can influence 

brain connectivity in order alleviate the 

harshness of premature birth and to further 

improve our care. 

Good sleep, healthy brains 

When babies sleep, their brains are actively 

developing. A preterm newborn spends most of 

his or her time in ‘active sleep’ (REM sleep), 

which coincides with heightened synaptogenesis 

and brain plasticity. It’s difficult to 

visually recognize sleep stages in preterm 

infants. However, to optimize sleep (and to set 

up intervention studies) we’re studying ways to 

automatically detect sleep stages. To do this, 

we’re using deep learning algorithms to 

recognize neonatal sleep stages based on 

monitor values. And together with two technical 

Universities (Delft and Eindhoven) we’re developing 

advanced wireless biomedical sensors 

(e.g. low frequency radar devices) to record 

sleep stages. 

Personalizing treatment 

Within our team, we’ve improved current 

neuroprotective treatments. One example is 

therapeutic hypothermia for infants with 

hypoxic-ischemic encephalopathy, and we’re 

optimizing patient selection for this treatment 

by studying pharmacokinetics of neurotropic 

medication. Additional therapies are also 

explored (Benders). 

The foundation for optimal brain development 

starts peri-conceptionally and lasts well beyond 

the teenage years. This calls for an interdisciplinary 

approach and together with our 

national and international colleagues, we’re 

improving the long-term neurodevelopmental 

outcome for infants with challenges in longterm 

brain development. We’re proud that our 

investigations can contribute to new European 

standards of care (e.g. ENCFI standards) and we 

benchmark our outcome using the International 

Consortium for Health Outcomes Measurements 

(ICHOM) standards. 

 

Floris Groenendaal, 

MD, PhD is a neonatologist 

whose goal is to improve 

diagnostics of early brain 

injury, using MRI/MRS and 

aEEG. In collaboration with 

the Laboratory of 

Neuro-immunology and 

Develop-mental Origins of 

Disease, UMC Utrecht, he’s 

explored novel neuroprotective 

strategies. Floris 

introduced therapeutic 

hypothermia in The 

Netherlands, and performed 

pharmacokinetics during 

cooling. 

Jeroen Dudink, MD, PhD 

is a neonatologist with 

expertise in neonatal 

neuroimaging. He studies 

the relation between 

neonatal sleep and early 

brain development. Together 

with technical Universities 

and commercial partners, he 

develops new devices to 

automatically recognize 

sleep stages. Furthermore, 

Jeroen studies the relation 

between neonatal cerebellar 

injury and long-term 

outcome. 

Better baby brains - 

the challenge goes on. 

- Floris Groenendaal 

fgroenen@umcutrecht.nl 

jdudink@umcutrecht.nl 



A brighter future for 

high-risk neonates 

mbenders@umcutrecht.nl 

Manon Benders, MD, 

PhD focuses on neonatal 

imaging of brain 

development and predicting 

outcome. She also 

investigates neuroprotective 

and neuro-regenerative 

strategies to reduce 

brain injury. 

The early years – starting from prebirth 

– is a critical period in a child’s 

development, as they form bonds with 

their parents, develop language skills 

and other cognitive functions, and 

establish behavioral patterns. Given the 

strong link between perinatal 

complications and adverse adolescent 

outcomes, we focus on developing 

interventions that may prevent, or at 

least reduce, perinatal life adversities. 

We have an outstanding Neonatal 

Neurology team that specializes in the 

development of objective biological 

measures in the developing brain in 

relation to long-term outcome (lifespan 

approach). We’ve established an 

integrated approach to study this, and 

by combining basic and translational 

developmental neuroscience, neuromonitoring 

and MRI analysis, we’ve 

developed perinatal neuro-protective 

and neural rescue strategies for the 

human fetus and infants. Because of our 

strong collaborative approach, we’ve 

became an internationally recognized 

center of expertise by the Committee of 

Rare Diseases of the National Federation 

of University Hospitals in the Netherlands 

and are part of the EpiCARE, a European 

Research Network for rare and complex 

epilepsies. 

CRUCIAL clinical trial 

There is an urgent need for 

neuroprotective strategies for infants 

with congenital heart disease (CHD) as 

they often experience long-term 

neurodevelopmental impairments. 

Perinatal 

improvement 

is multiplying 

health gain 

later on. 

- Manon Benders 

To investigate this, we recently launched a 

multicenter CRUCIAL-trial (CeRebrUm and 

Cardiac protection with Allopurinol) in 

neonates with CHD who require cardiac 

surgery with cardiopulmonary bypass. 

We’re investigating the effects of postnatal 

and perioperative allopurinol 

administration on postoperative brain 

injury in CHD neonates. Patients will be 

screened using fetal MRI and included 

before birth, requiring extensive 

collaboration with obstetricians, 

neonatologists, cardiologists, pediatric 

intensivists and pediatric thoracic 

surgeons. Our primary outcome is based 

on fetal, postnatal and post-operative MRI 

analysis in close collaboration with 

quantitative MRI analysts at the Image 

Sciences Institute, UMC Utrecht. Longterm 

outcome is a secondary objective of 

this study, evaluated by psychologists and 

occupational therapists, for which we 

collaborate with pediatric rehabilitation 

and psychiatry. Additional therapies are 

also explored within our team 

(Dudink and Groenendaal). 

In addition to our goals of improving 

long-term outcome in high-risk neonates, 

we subscribe to the philosophy of open 

science. Through the YOUth study 

(uu.nl/youthcohort), a large longitudinal 

cohort study that collects information 

about brain and behavioral development, 

we’re able to broadly share anonymous 

information about our healthy and highrisk 

neonates. 

Big Data for small Babies 

Premature babies admitted to the 

neonatology intensive care unit are closely 

monitored as they are susceptible to 

infection. Over the past decade, we’ve 

collected a vast amount of data and a 

group led by Daniel Vijlbrief, PhD, uses 

machine learning on this data in order to 

improve diagnosis and treatment options 

regarding sepsis for preterm babies. 

Preparing our future talent 

Within our team, we have a culture of 

collaboration and this extends to young 

clinicians and researchers with high 

potential. They have opportunities to learn 

and train through our educational 

programs and to contribute to our overall 

societal impact through our outreach 

activities. Our multidisciplinary approach 

will lead to earlier diagnosis, tailored 

treatments and enable us to create new 

and better interventions to transform 

children’s lives. 


Protecting 

fertilityFor many, 

parent is one of the happiest 

days in life. Unfortunately, 

1 in 6 couples who want to 

conceive, fail to do so. This 

infertility has many different 

causes and we focus on 

reduced ovarian reserve 

and late effects of childhood 

cancer treatment. 

becoming a 

 

Helen Torrance and Frank Broekmans 

work at the Center for Reproductive 

Medicine which is an international 

and national expert center and global 

leader in the field of reproduction. 

Both care and research are aimed at 

optimizing the chances of a healthy 

conception and thereby the chances 

of a healthy child. 



Helen Torrance MD, 

PhD specializes in 

reproductive medicine. 

She combines clinical 

and scientific research 

related to fertility. 

Her current interests 

include future fertility 

for children with 

chronic disease and 

optimizing successful 

implantation. 

htorranc@umcutrecht.nl 

Changing IVF protocols 

Ovarian ageing and reduced ovarian reserve have been a main topic of 

research at the Center for Reproductive Medicine for more than 20 years, 

and we’ve answered many diagnostic, prognostic, etiologic and therapeutic 

questions. One of our most recent multicenter randomized controlled trials 

studied the efficacy of individual hormonal treatment for IVF. We 

demonstrated that high doses of hormones in women with a reduced 

ovarian reserve actually do not increase her chances of having a baby. 

Our findings have helped change long-standing IVF practice in which 

high-dose hormones were prescribed for infertility. This is especially 

important as there are concerns that IVF impacts the long-term health of the 

children conceived through this technique. Although still unclear, 

high hormone doses may be a causal factor. 

Caring for the entire reproductive life cycle 

Ovarian ageing can have a clear cause, be idiopathically or be iatrogenically 

caused by, for example, cancer treatment. We collaborate with the Princess 

Maxima Center to provide both care and research for children with cancer, 

focusing on early fertility counselling and fertility preservation. 

can be devastating. 

We’re Infertility 

improving care for these 

patients so more people can enjoy 

the exceptional path of parenthood. 

- Helen Torrance 

This type of lifecycle medicine and care is also important for children with 

other childhood diseases that used to be lethal but are now considered 

chronic diseases. These children need follow-up care directly related to their 

condition and sadly, disease progression and exposure to medication during 

childhood and adolescence may affect their reproductive system. 

More research into current and future fertility of these patients is needed. 

Mapping out infertility 

If patients have concerns about future fertility, then fertility counselling and 

fertility preservation should be offered to all individuals at risk as becoming 

a parent may significantly contribute to a long-term improved quality of life. 

From 2019 onwards, we expect to complement existing long-term child 

health follow-up databases with fertility parameters so that early 

determinants can be connected to late fertility outcome. Our team will start 

by including girls with chronic hematologic conditions (for example, 

Diamond Blackfan anemia, sickle cell anemia or thalassemia; in collaboration 

with the department of haematology (Bartels) and will then extend this 

concept to other childhood diseases. 

Frank Broekmans 

MD, PhD is devoted to 

the mysteries behind 

ageing ovaries. He 

focuses on assessing 

fertility in childhood 

disease survivors with 

the goal of preventing 

early life onset genetic 

disease. His group 

conducts Preimplantation 

Genetic Diagnostic 

testing of embryos 

created by Assisted 

Reproductive 

Technology. 

fbroekma@umcutrecht.nl 

time to be proactive - to provide 

preventative It’s 

care for infertility and 

to avoid reproductive consequences 

of childhood disease. - Frank Broekmans 


CONGENITAL AND HEREDITARY DISORDERS 

ghaaften@umcutrecht.nl 

Finding genetic 

variations 

 

Your DNA 

at the 

center of 

care. 

- Hans Kristian 

Ploos van Amstel 

Gijs van Haaften, 

PhD focuses on 

understanding 

the genetics and 

biology of monogenic 

disorders, with 

a focus on metabolic, 

craniofacial and 

cardiac disorders. 

Genetic testing can identify 

aberrations and changes in our 

genetic information. This can 

help confirm or rule out 

suspected genetic diseases, it 

can identify hereditary genetic 

conditions and determine 

whether an unborn infant has 

a certain disorder. With the 

event of advanced genome 

sequencing technologies, 

genetic testing is becoming 

more routine in medical care. 

The Department of Genetics within the 

Child Health Program focuses on 

developing technologies for genetic 

diseases, in particular, on genome-wide 

detection of genetic variations. We aim to 

establish the relationship between 

clinical presentation, gene expression 

and protein function of both morbid 

genes (genes that are causally linked to 

disease) and candidate morbid genes. 

To address this, two national cooperative 

studies have been initiated and Hans 

Kristiaan Ploos van Amstel leads the 

diagnostic lab. 

WGS-based approach to 

understanding genetic diseases 

Whole genome sequencing (WGS) 

can identify almost all disease-causing 

mutations and has broad applicability in 

diagnostics, treatment and drug response. 

It has been therefore hypothesized 

whether a “one-test-fits-all” could be 

implemented to diagnose rare genetic 

disorders. This would increase diagnostic 

yield in a shortened time frame, reduce 

complexity and costs, result in early access 

to personalized patient care and reduce 

co-morbidity and mortality. We’re 

currently performing a study with patients 

from the neonatal intensive care unit and 

with neurodevelopmental disorders. 

A new blood test for prenatal 

genetic diagnosis 

Our second study is in collaboration with 

Wouter de Laat, PhD at the Hubrecht 

Institute. Together, we’ve developed 

a Monogenic Non-Invasive Prenatal 

Diagnosis (MG-NIPD), a new highly 

sensitive blood test, to detect 

monogenetic disorders during the early 

stages (8-10 weeks) of pregnancy. 

MG-NIPD can detect genetic diseases 

that have a small genetic variation, and 

may replace traditional, more invasive 

methods such as amniocentesis and 

chronic villus sampling. We’re currently 

validating and optimizing the MG-NIPD 

in at-risk families as a safe and reliable 

alternative for prenatal diagnosis. 

Understanding the biology of 

genetic disease 

For many genetic diseases, the precise 

genetic cause is not understood, and by 

studying genes and their functions in 

human health and disease, we gain 

insights into patient care and novel 

biological processes. We focus on the 

biology and genetics of rare diseases, 

with a particular interest in metabolic, 

craniofacial and cardiac anomalies; 

this area of investigation is led by 

Gijs van Haaften. 

A recent example is the discovery that 

germline mutations in histone H4 cause 

a developmental syndrome by altering 

DNA damage response and cell cycle 

control. We model patient mutations to 

study effects on gene and protein 

function, and use several approaches 

including patient cells, cell lines in 

which we introduce the patient-specific 

mutated allele and the zebrafish 

developmental model. 

We recently described a method to 

engineer the zebrafish genome at the 

single nucleotide level, using the geneediting 

technology CRISPR/Cas9 in 

combination with homology-directed 

repair. This allows us to generate precise 

models for human genetic disorders. 

We’re currently investigating whether 

certain therapies can reverse 

cardiovascular defects with the goal of 

translating our findings to patients 

in the future. 

jploos@umcutrecht.nl 

Hans Kristian 

Ploos van Amstel, 

PhD focuses his 

research on impro - 

ving detection and 

interpretation of 

genomic variations 

and on identifying 

disease genes. 

He strives to 

diagnosis, prognosis 

and treatment. He is 

chair of the Dutch 

Society for Clinical 

Genetic Laboratory 

Diagnostics (VKGL). 



truly connected 

interdisciplinary 

Our 

network 

enables swift transition 

from bedside to bench 

and back, directly 

supporting improvement 

of care for vulnerable 

patients. 

- Marc Lilien 

Kidney 

and Urinary tract 

An end stage renal disease patient is 

referred to the outpatient clinic for 

hereditary renal disease: The patient is 

diagnosed with an autosomal dominant 

renal disease. Recently, his first child was 

born with an autosomal dominant renal 

disease. This does not recur in a kidney 

graft. His eldest (at 50% risk) was 

subsequently evaluated at the pediatric 

hereditary renal disease outpatient clinic. 

Wishing to further establish their family, 

the couple was informed about their 

options and chose to try to conceive using 

preimplantation genetic diagnosis. 

aeerde@umcutrecht.nl 

mlilien@umcutrecht.nl 

Albertien van Eerde 

MD, PhD is clinical 

geneticist at the UMC 

Utrecht who specializes 

in nephrogenetics. She’s 

the coordinator of the 

Expert Center for 

Hereditary and Congenital 

Renal and Urinary 

Tract Disorders, which is 

accredited both 

nationally and by the EU 

(through ERKNET). 

Marc Lilien MD, 

PhD is a pediatric 

nephrologist at the 

Wilhelmina Children’s 

Hospital and has 

expertise in renal 

ciliopathies and renal 

tuberous sclerosis 

phenotypes. 

Our research in the kidney and urinary tract 

focuses on clinical expertise in the nationally 

accredited Center of Expertise for Hereditary and 

Congenital Nephrologic and Urologic Disorders. 

The Expert Center ensures optimal care and 

research for families with renal disease and spans 

infancy to adulthood, including preconception 

and prenatal care. It encompasses (pediatric) 

nephrology, (pediatric) urology, clinical and 

laboratory genetics, obstetrics, nephropathology, 

radiology, and we participate in ERKnet: 

the European Reference Network for Rare 

Kidney Disease. 

The case above is a good clinical example of the 

interdisciplinary nature of our work. When a 

diagnosis is challenging or undetermined, we 

incorporate genetic testing and functional follow 

up. This has proven effective for the ITGA3 gene. 

For insights into cystinosis-related phenotypes, 

we collaborate with Roos Masereeuw, PhD at 

Utrecht University who is an expert on how 

pharmacologics affect molecular pathways, and 

to further investigations into new candidate 

genes we collaborate with the Antignac’s group 

in Paris. 

We also perform cohort-based research. Albertien 

has shown that NPHP1 gene deletions can cause 

adult renal disease, which comprises about 0.5% 

of adult end stage renal disease at all ages. This 

challenges the paradigm that nephronophthisis is 

primarily a pediatric renal disease, and has 

consequences for follow up into adulthood and 

kidney donation, especially by siblings. We both 

actively participate in the AGORA cohort (for 

example, patients with congenital anomalies of 

the kidney and urinary tract and renal ciliopathies). 

Marc has recently published a detailed overview 

of renal ciliopathy phenotypes, and steps towards 

early biomarkers. 

With a recently acquired Dutch Kidney Foundation 

grant, Albertien will further establish a registry of 

patients with rare renal diseases, and will build a 

Kidney Gene Regulatory Network. We both also 

want to further the understanding of “renal 

sensitivity”: What drives the variability in severity 

in patients with similar genetic predisposition or 

toxic exposure. 

Genetic diagnoses have an effect in the full circle 

of life. And they are too often missed, especially in 

adult nephrology. Together, our research activities 

create synergy and we’re able to create impact for 

instance, by developing informational material 

(like online movies) for patients, by conceiving a 

national guideline for genetic testing in (pediatric) 

nephrology and by teaching pediatricians, 

nephrologists and geneticists, nationally and 

internationally. We often work together with the 

Dutch Kidney Patient Association. 


Congenital and genetic 

heart disorders 

Roughly 1 in 100 children 

have a congenital cardiac 

abnormality and about 1 

in 200 individuals have a 

gene mutation predisposing 

him or her to an inherited 

cardiac disorder including 

a cardiomyopathy or 

arrhythmia syndrome. 

More and more genes and 

mutations underlying these 

different cardiac disorders 

have been identified. Our 

departments of Genetics 

and Pediatric Cardiology 

are focused on elucidating 

these genetic defects and 

our discoveries advance 

both patient and family 

care, as well as research. 

Congenital heart 

defects have the 

highest prevalence 

of all congenital 

defects. 

- Hans Breur 

 

hbreur@umcutrecht.nl 

Hans Breur MD, PhD 

Pediatric cardiologist is 

one of the founders of 

the Congenital Heart 

Disease LifeSpan 

Program in which all 

patients with severe 

congenital heart disease 

undergo extensive and 

lifelong cardiac and 

neurocognitive 

follow-up, and where 

interventions are 

developed to improve 

outcome. 

In patient and family care, the results of a 

genetic test can be used for genetic 

counseling as it provides important 

information on inheritance patterns and 

aids with determining recurrence risk 

with a potential for prenatal diagnostics. 

In cases of a late onset autosomal 

dominantly inherited disease, 

presymptomatic genetic testing 

(where a genetic mutation may be 

detected before an individual presents 

with clinical symptoms) in family 

members can be facilitated with these 

genetic discoveries. Given the autosomal 

inheritance, this may lead to 50% fewer 

family members who require follow-up 

by a cardiologist. 

Unfortunately, clinical variability is still 

poorly understood: Individuals with an 

identical mutation can be symptomless 

for decades while close family members 

may encounter signs of the disease at an 

early age. And we still don’t know which 

factors contribute to disease 

development at what phase in life. Our 

researchers and clinicians collaborate 

with several patient organizations and 

together, we’re identifying factors that 

influence the development and 

progression of these disorders. From this, 

we can better determine risk and develop 

personalized treatments. In our 

diagnostic and therapeutic work-up we 

use cutting edge imaging techniques like 

3-D rotational angiography. 

Organizing our data 

In the Netherlands we closely collaborate 

with all other centers involved in 

Congenital and Cardiogenetic Disease 

within the Dutch National Working Group 

on cardiogenetic diseases. 

Within this multidisciplinary network of 

clinical and molecular geneticists, 

cardiologists, pediatric cardiologists and 

pathologists, we aim to improve 

diagnostics and care for these patients. 

We’ve initiated several large-scale patient 

registries, including the national 



jtintel3@umcutrecht.nl 

Peter van Tintelen, 

MD, PhD 

Chair, Department of 

Genetics 

is a clinical geneticist 

who set up cardiogenetics 

research at 

the UMC Groningen. In 

2018, he returned to 

Utrecht to become 

Chair of the Department 

of Genetics. The 

main focus of his 

research is understanding 

clinical variability 

in inherited cardiac 

disease. 

The worldwide impact 

of congenital heart disease is 

greater than cancer when 

looking at years lost to disability. 

Arrhythmogenic Cardiomyopathy Registry 

(www.acmregistry.nl) which contains data 

from over 1000 patients and family 

members, and the PLN Cardiomyopathy 

Registry, which has enrolled over 800 

patients who carry an identical mutation. 

Using these data, we’re able to improve 

risk prediction for patients and 

their families. 

Lifelong care for our patients 

All patients with a severe congenital 

heart defect enroll in our Congenital 

Heart Disease Life Span Program. In this 

program, life-long structured cardiac 

and neurocognitive follow-up starting 

from pre-natal diagnosis onwards, is 

combined with an extensive research 

program including blood and tissue 

biobanking for all patients. A stateof-the-art 

pipeline including whole 

One in 250 children have a 

mutation predisposing for 

an inherited cardiomyopathy 

or arrhythmia syndrome. 

- Peter van Tintelen 

genome sequencing and zebrafish 

modeling (together with the Hubrecht 

institute) allows us to study the origin of 

congenital heart disease. Patients with 

inherited cardiomyopathies and 

arrhythmias enroll in our multidisciplinary 

life cycle follow-up, where families are 

counselled and treated by both the adult 

and pediatric cardiologists as well as a 

clinical geneticist. 

With current excellent survival rates, 

our focus needs to shift from mortality 

to quality of life. 

- Hans Breur 


Better care for the rare 

Gastroenterology - Hepatology - Metabolic Diseases 

Metabolic diseases comprise a group of more than 1000 rare genetic diseases in which 

a metabolic pathway is perturbed. These conditions often have devastating 

consequences for patients and their families, and may involve a diagnostic odyssey, 

prognostic uncertainty and absence of treatment options. Our multidisciplinary 

research, in which laboratory and clinical scientists closely collaborate, aims to increase 

knowledge on these diseases in a number of ways. 

 

Let’s make use of 

the unprecedented 

technological possibilities 

to improve 

patient care in 

terms of diagnostics 

and (personalized) 

therapies. 

- Sabine Fuchs 

Disease discovery 

In undiagnosed patients with a 

metabolic phenotype, whole exome 

sequencing, metabolomics and deep 

phenotyping are combined to elucidate 

existing and new defects. When we find 

a candidate gene with related changes in 

the metabolome or phenotype of a 

patient, we perform functional studies in 

cells or organoids from the patient or 

after CRISPR-Cas9 gene-editing or in 

animal models like the zebrafish to 

identify and characterize new genetic 

metabolic diseases. In recent years, we 

have collaboratively described two new 

defects in the malate aspartate shuttle, 

two defects in glutamate metabolism 

and a defect in ketone utilization. 

This approach has also elucidated 8 

inborn errors outside the classical 

boundaries of metabolism (STX3, 

NSMCE3, UNC13A, ANKZF1, PET117 

(complex iv), KIAA1109, TRAPPC2L, 

SMARCC2). In all families involved, these 

discoveries have led to long-awaited 

diagnoses and prenatal screening 

possibilities, and in some, to successful 

treatment of affected children. 

Pathogenesis of disease 

We focus on defects in vitamin B6 and 

amino acid metabolism. To pave the way 

for better treatments, our team 

investigates pathogenic mechanisms in 

these defects making use of deep 

phenotyping, metabolomics and model 

systems. We’ve published a zebrafish 

model of pyridoxine dependent epilepsy, 

a mouse model of pyridoxal phosphatase 

deficiency and a new cause of vitamin 

B6-dependent epilepsy: pyridoxal 

phosphate binding protein deficiency. 

Similarly, these strategies have 

contributed to the discernment and 

publishing of a common clinical 

phenotype for amino acid tRNAsynthetase 

deficiencies, putatively based 

on a common disease mechanism. 

Follow-up of treatment 

Patients with lysosomal storage disease 

can be treated with stem cell therapy. 

Although this can be successful, residual 

disease is substantial. To address this, we 

make use of a unique standardized 

multidisciplinary follow-up facility 

(Sylvia Toth Center; also used for deepphenotyping) 

to investigate the natural 

history of these diseases, and clinical and 

biochemical follow-up of patients who 

have been transplanted. Examples of 

novel biochemical markers include the 

analysis of iduronidase in blood spots 

and saliva, analysis of glycosaminoglycans 

in tear drops by mass spectrometry and 

analysis of vacuoles in lymphocytes as a 

marker for neuronal ceroid lipofuscinosis. 

Organoid research 

In close collaboration with groups at the 

Hubrecht Institute, we generate liver and 

intestinal organoids from patient-derived 

adult stem cells. These organoids 

represent a unique patient-specific in 

vitro model that we use to elucidate 

disease mechanisms, develop novel 

therapeutic strategies (including 

organoid transplantations) and test these 

strategies in a personalized manner. 

This led to the identification of novel 

causes of secretory diarrhea (due to 

deficiencies of STX3 and DGAT1). 

Furthermore, we’re in the process of 

evaluating small molecule therapy for 

genetic cholestatic diseases, such as 

progressive familial intrahepatic cholestasis. 



nverhoev@umcutrecht.nl 

Nanda Verhoeven 

PhD has a special 

interest in disorders 

of vitamin B6 and amino 

acid metabolism and 

the discovery of new 

diseases in this area. 

Nanda is Head Laboratory 

Metabolic Diseases. 

sfuchs@umcutrecht.nl 

Sabine Fuchs MD, 

PhD is a pediatrician in 

metabolic diseases, 

pharmacist and basic 

scientist with a lab in 

the Hubrecht institute, 

with the aim to improve 

care for patients with 

metabolic/liver diseases 

by unraveling disease 

mechanisms (in patient 

derived organoids) to 

develop and test novel 

treatment strategies, 

including liver stem cell 

transplantations. 

phassel2@umcutrecht.nl 

Peter van Hasselt MD, 

PhD focuses on translational 

research aimed at 

creating 'better care for 

the rare' by 1) elucidating 

the genetic cause; 2) 

describing effects of 

treatment on the natural 

disease course; 3) 

improving early recognition 

and/or preventive 

measures; and 4) 

creating novel diseaseseverity 

markers. 

jjans@umcutrecht.nl 

Judith Jans PhD 

focuses on the development 

and introduction of 

untargeted metabolomics 

in diagnostics to 

elucidate novel genetic 

metabolic diseases and 

improve current 

diagnostic practice. She 

aspires to fully integrate 

genomics and metabolomics 

data to advance 

patient care. 

 

Ask yourself how the present 

situation compares to your ideal 

situation, and how it helps you 

see how to decrease the gap. 

- Peter van Hasselt 

 

A solid diagnosis 

is the foundation 

on which care and 

treatment can 

be built. 

- Nanda Verhoeven 

In our labs, technology development is a 

driving force for the above-mentioned 

projects. We’ve developed a direct 

infusion high-resolution mass spectrometric 

pipeline for untargeted metabolomics. 

We’ve validated this approach 

in blood spots and plasma from a number 

of patients with known genetic metabolic 

diseases and demonstrated that this 

method is capable of correctly 

establishing diagnoses. This approach is 

promising for disease discovery, 

identification of biomarkers and for 

research on pathogenic processes. In 

addition, we employ frontline geneediting, 

organoid technologies and 

animal models for in vitro modeling. The 

strong clinical embedding, with an 

interest in patients with novel genetic 

metabolic defects, deep phenotyping 

and use of the human phenotype 

ontology informs our research on the 

clinical presentation and natural course 

of known and novel disease entities. 

In the Netherlands, we collaborate with 

the five other University Medical Centers 

in a national initiative, United for 

Metabolic Diseases. This multidisciplinary 

consortium consists of pediatricians, 

internists, clinical geneticists, laboratory 

specialists and scientists in the field of 

genetic metabolic disease and patient 

organizations. We aim to improve 

registration, education, technology and 

e-health and to find a diagnosis for 500 

undiagnosed patients, both children and 

adults, by combining multi-omics 

technologies and bioinformatics. The 

first patients were included in 

March/May 2019. 

 

Significant 

advances in 

diagnostics can 

be made when 

we successfully 

combine the 

diverse strengths 

of metabolomics 

and genomics. 

- Judith Jans 


SEVERE INFLAMMATORY DISORDERS 

Cystic Fibrosis: 

personalized treatment 

for all patients 

 

We are honored to be 

selected to participate in the 

HIT-CF Europe consortium and 

join forces with key thought 

leaders to explore the potential of 

a personalized medicine 

approach as a possible new 

frontier for CF therapy. 

- Meenu Chhabra, President and Chief 

Executive Officer of Proteostasis 



The UMC Utrecht hosts the largest 

expertise center for Cystic Fibrosis (CF) in 

the Netherlands, giving care to about onethird 

of more than 1500 Dutch CF 

patients. Our multidisciplinary team, led 

by Kors van der Ent, MD (pediatric 

pulmonologist) and Harry Heijerman, MD, 

PhD (adult pulmonologist) covers the 

entire spectrum of care from heel prick 

screening to lung transplantation. In 

addition, we have our own clinical research 

team, which supports investigator-driven 

and pharmaceutical-driven clinical trials. 

These trials have focused on treatment of 

pulmonary inflammation and infection 

(microbiome studies) and on the effects 

of CFTR-modulators. 

Chloride Concentration and intestinal current 

measurements. 

Organoids in drug discovery 

Preclinically, organoids are used to identify and 

develop CFTR-modulating drugs and to explore 

mechanisms associated with differences in CFTR 

function. Pharmaceutical companies use intestinal 

organoids in their drug development pipeline 

and initial high-throughput-screening has 

resulted in the discovery of different chemical 

structures as potential CFTR-modulating drugs. 

Organoids are used to test both the potency of 

single drugs and to compare the efficacy of 

combination treatments. Our group also 

highlighted the translational potential of 

organoids, demonstrating that genotype-specific 

effects of CFTR-modulators correlate with clinical 

trial data at group level. 

Our CF Center leads the cystic fibrosis core 

network of the European Reference Network 

LUNG (ERN-LUNG), a network of European 

healthcare providers dedicated to ensuring and 

promoting excellence in care and research for the 

benefit of patients affected by rare respiratory 

diseases. We’re also a member of the Clinical Trial 

Network of the European CF Society, and have 

participated in the European CF Patient Registry 

for more than 10 years, enabling quality control 

and studying long-term patient outcomes. 

A formal collaboration agreement between the 

UMC Utrecht and the Dutch CF Patient 

organization was signed in 2016 and joint 

initiatives between patients and caregivers have 

been developed. 

Organoid technology 

Our CF Center Utrecht has its own research lab 

headed by Jeffrey Beekman, PhD, and the close 

collaboration between basic science and clinical 

care in Utrecht has led to a highly translational 

research profile. His research group developed an 

adult stem cell-based culture and assay 

technology (organoids) to model human 

pulmonary disease and in particular, CF. 

Organoids are three-dimensional, multi-cellular 

structures that recapitulate tissue features of the 

parental organ and are usually grown from donor 

tissue fragments. As organoids are functional 

expressions of individual genomes, they’re 

particularly useful for understanding how genetic 

factors contribute to individual disease. Intestinal 

organoids have been at the forefront of these 

developments as culture methodology was first 

developed for this tissue source. For CF, human 

intestinal organoids can be grown from intestinal 

crypt fragments isolated from rectal biopsies. 

We’ve shown that organoid measurements reflect 

residual CFTR function and correlate with 

predicted severity of the CF genotype and other 

biomarkers of CFTR function, including Sweat 

Promising drug treatments for CF 

Recent proof-of-concept in two patients with 

ultra-rare mutations showed clear in vitro-in vivo 

correlation in response to treatment with the drug 

ivacaftor. A subsequent study found that intestinal 

organoid measurements with the drugs curcumin, 

genistein, ivacaftor and lumacaftor/ivacaftor 

correlated with in vivo responses in pulmonary 

function and sweat chloride concentrations on the 

individual level. These techniques have 

revolutionized CF care, especially in patients with 

ultra-rare mutations. New mutation class-specific 

drugs are currently only being tested in patients 

with well-described, very common mutations. 

As a result, market authorization and 

reimbursement of these drugs is only granted in 

these specific subsets of patients. Nevertheless, 

other patients with less common mutations might 

also benefit from them. 

Using organoids to predict 

treatment response 

In our group, Kors coordinates an EU-funded 

consortium study (www.HITCF.org) which aims to 

develop a path for access to therapies for 

individual patients or patient groups who show 

positive response to the therapy in an organoid 

test, and to pave the way for organoid-based 

personalized medicine. Our organoid studies in 

CF focus on pre-treatment selection of patients 

with ultra-rare CFTR-variants and biopsies of 

patients with ultra-rare CFTR mutations are 

collected all over Europe and bio-banked in 

Utrecht. Currently four pharmaceutical companies 

deliver their lead CFTR-modulating compounds 

for screening and ultimately clinical trials in 

pre-selected patient groups are foreseen, in close 

collaboration with the European Medical Agency 

and MoCA (Mechanisms of Coordinated Access 

to Orphan Medicinal Products). 


jbeekman@umcutrecht.nl 

Kors van der Ent, 

MD, PhD initiated the 

CF-Center Utrecht in 

1997. He is a co-developer 

of the Utrecht 

organoid model for CF. 

Kors is coordinator of 

the H2020 HIT-CF 

program and core 

network leader for CF 

in the European 

Reference Network 

(ERN-LUNG). 

Jeffrey Beekman, 

PhD heads a research 

program focused on 

development of 

personalized medicine 

for CF. His work aims 

to develop new 

diagnostics and 

therapeutics to enable 

individually optimized 

treatments. 


We are extremely excited to be 

participating in the HIT-CF research 

project, which has the potential to 

lead to treatment options for many 

CF patients, based on their 

 

functional responses in the lab. 

- Dr. Gregory Williams, Chief Operating Officer, Eloxx Pharmaceuticals 

The patient not only 

thinks along, but 

decides. The patient 

perspective must be 

considered for care 

and research. 

What is important 

for CF patients and 

what research is 

needed? 

- Jacquelien Noordhoek, Director, 

Dutch CF Foundation 

Ethics 

and innovation 

are natural partners, 

In fact, you would like 

doctors and researchers to 

always think about the ethical 

and social impact of their 

innovation at an early stage. 

 

Patients can think along about the design 

of the technology and become 

co-designers. 

- Annelien Bredenoord, Professor, 

Ethics of Biomedical Innovation 

My experience gave me new insights. For example, how important it is for doctors to express 

their confidence in me as a parent. As a mother you are defeated and powerless, you dare not 

attach yourself for fear of loss. It is also very supportive if the doctor fulfills the role of a mental 

coach and encourages you. Parents must play a central role; parental love is the best medicine. 

Benjamin is now eight years old. He is healthy and goes to school. I often drive past the 

Wilhelmina Children's Hospital - and I always have a deep sense of gratitude. 

- Anne Marie Louwerse, mother of Benjamin, who was born at barely 25 weeks. 

 

~ 



Inflammatory 

Bowel Disease 

Inflammatory bowel disease (IBD) is a complex disorder associated with a 

dysregulated immune response to environmental triggers in a genetically 

susceptible host. The incidence of IBD is increasing around the world: 

Approximately 25% of patients with IBD present before the age of 20, with an 

annual pediatric incidence of 0.5 to 23/100,000 person-years in Northern and 

Western Europe. The cause of this increase is poorly understood, but proposed to 

include increased antibiotic use, changes in diet and the adoption of prepared 

foods that include emulsifiers and surfactants, all of which contribute to 

alterations in the gut microbiome. 

Saskia van Mil, 

PhD Associate 

Professor 

studies the roles 

of microbiota, bile 

acids and their 

receptors in health 

and chronic 

infla-mmatory 

diseases, e.g. 

Inflammatory 

Bowel Disease 

and non- alcoholic 

steatohepatitis. 

smil2@umcutrecht.nl 

Small bugs can make a big difference 

In children with Crohn’s disease, exclusive 

enteral nutrition is the therapy of choice for 

remission induction with remission rates 

comparable to steroids, indicating that nutrition 

plays an important role in IBD activity. Even 

though several dietary factors have been 

implicated in the pathogenesis of IBD, their 

relative importance and exact role is unknown. 

Current research on the interactions between 

food, microbiome and IBD are based on crosssectional 

cohort studies, which do not catch the 

changes in diet and microbiome prior to the 

development of an IBD flare. In addition, 

microbiome research has focused on the 

difference in the microbial species between IBD 

patients and controls, and in IBD patients in and 

out of an inflammatory episode. The most 

imminent questions that we are currently 

investigating are: what are the metabolic 

functions of these differentially present 

microbes, how do those functions affect host 

metabolism and IBD activity and what are the 

effects of dietary changes? 

Our research contributes to the cycle of life 

theme of Child Health, by gaining a better 

understanding of the nutrition-microbiome-bile 

acid-host health axis, and pursuing development 

of non-invasive biomarkers and novel therapies 

for IBD. 

acids act as 

hormones Bile 

and dictate 

microbiome composition 

and host metabolism. 

- Saskia van Mil 

25% IBD cases 

diagnosed during 

Childhood 

A potential therapeutic target 

In addition, our previous work has contributed 

to our current knowledge on bile acids as a 

treatment target for IBD. Bile acids activate the 

bile acid receptor FXR, which regulates the fate 

of dietary components; it also counteracts 

inflammation and controls the composition and 

abundance of gut bacteria. In IBD patients, the 

expression and function of FXR is suppressed. 

In collaboration with TES Pharma, we’re 

developing tissue and gene-selective FXR 

ligands for the treatment of IBD. 

Up to 1 in 4 cases of IBD are 

diagnosed during childhealth 

6x 

To develop 

More 

likely 

Colorectal 

cancer 

IBD patients are six times 

more likely to develop 

colorectal cancer. 


RSV & Rotavirus: 

so much in common 

Translational 

research is 

needed to 

improve the 

health of 

children. 

- Louis Bont 

 

lbont@umcutrecht.nl 

Louis Bont, MD, PhD 

has an interest in understanding, 

preventing and treating 

respiratory syncytial virus 

(RSV) bronchiolitis. He was 

one of the founders of the 

TULIPS program, which 

furthers the career of 

multidisciplinary early stage 

researchers in the field of 

child health. 

Infant mortality is a major global health threat and the most 

prevalent clinical syndromes are diarrhea and respiratory 

infection. According to a Global Burden of Diseases study 

conducted by the Institute for Health Metrics and Evaluation 

at Washington University, rotavirus and respiratory syncytial 

virus (RSV) are the primary causes of infant diarrhea and 

infection, respectively. 

In a retrospective case series, we’ve demonstrated that indeed, most children 

dying from an RSV infection are younger than 6 months of age. The World Health 

Organization has prioritized vaccine development for rotavirus and RSV infections; 

rotavirus vaccines have now been introduced and it’s expected that RSV vaccines will 

soon follow. 

RSV is the 

second 

cause of 

death 

during 

infancy 

worldwide 

Within the Child Health Program, we also prioritize rotavirus and RSV, which have 

much in common. Both are RNA viruses with exclusive tropism for the epithelium. 

Although each virus itself is genetically diverse, it appears that, while genetic diversity 

is needed to escape the immune system, it doesn’t contribute to disease severity. 

Children with co-morbidities, such as preterm birth, have the highest risk of a severe 

course of disease, including death. 

Developing a vaccine is complicated 

Viruses are excellent at evading our immune system, which makes developing an 

effective vaccine challenging. An early formalin-inactivated RSV vaccine developed 

the 1960s was a disappointment. Rather than prevent infection, it augmented RSV 

disease in vaccine recipients upon natural infection in the community; two immunized 

infants died upon infection and the clinical trial was abruptly ended. Several decades 

later, the first rotavirus vaccine Rotashield® was approved for infant gastroenteritis. 

Unfortunately, it increased susceptibility to intussuception, a rare form of bowel 

obstruction where the bowel folds upon itself. Upon investigation, it was concluded 

that Rotashield® did contribute to or increased the risk of intussuception and the 

vaccine was withdrawn from the market. 



Viruses also infect older patients 

RSV and rotavirus infections also cause severe disease throughout life. 

An RSV infection during infancy is associated with recurrent wheeze and asthma. 

We conducted a multicenter, double-blind, randomized placebo-controlled MAKI 

clinical trial and showed that RSV is causally-related to infant wheeze. In older 

adults, RSV is associated with similar incidence and severity compared with 

influenza. Rotavirus can cause acute gastroenteritis throughout life, but is especially 

severe in immunocompromised adults and frail elderly. In general, increased 

awareness of severe RSV and rotavirus infection in adults is needed. 

pbruijni@umcutrecht.nl 

Patricia Bruijning, MD, 

PhD focuses on vaccinepreventable 

diseases, which is a 

central theme in epidemiological 

research. She aims to 

optimize vaccination strategies 

for infants and children with a 

special focus on medicallyvulnerable 

pediatric 

populations. 

It takes a village 

Our aim in Child Health is to contribute to the development and implementation of 

vaccines against RSV and rotavirus. We conduct our research as part of large 

national and international consortia, including RIVAR, RESCEU, ReSViNET and RSV 

GOLD. The RIVAR-program (Risk-Group Infant Vaccination against Rotavirus) aims to 

implement a hospital-based rotavirus vaccination program for high-risk infants; 

the IMI-funded RESCEU project informs the European Union of the RSV burden in 

Europe before future introduction of RSV vaccines; Louis Bont is the founding 

chairman of the ReSViNET Foundation, which brings together a global network of 

stakeholders in order to decrease the vurden of RSV infection; and The Bill and 

Melinda Gates Foundation-funded RSV GOLD project studies clinical characteristics 

of children dying from RSV infection. By defining age distribution of RSV-related 

deaths we can guide impact analysis of future maternal RSV vaccines. 

Together with our collaborators in other areas, including Linde Meyaard, PhD 

(immune dysfunction in HIV), Jeanette Leusen, PhD (therapeutic antibodies) and 

Jose Borghans, PhD (leukocyte dynamics), we’re characterizing virus transmission 

dynamics and conducting health economic evaluations of vaccination strategies. 

We’re gaining a better understanding of disease pathogenesis, and developing 

effective and affordable preventive interventions and immunodiagnostic tools. 

 

Prevention is better than treatment. 

- Patricia Bruijning 


Pediatric Rheumatology: 

Collaboration is essential 

The Pediatric Rheumatology Department, Wilhelmina Children’s 

Hospital is comprised of both basic science and clinical research groups. 

These include a joint pediatric rheumatology research group, led by 

Bas Vastert, MD, PhD and Jorg van Loosdregt-Vastert, PhD; a translational 

immunology lab headed by Femke van Wijk, PhD; and research by several 

clinical pediatric rheumatology groups, including Joost Swart, MD, PhD, 

Nico Wulffraat, MD, PhD and Sytze de Roock, PhD (Juvenile Idiopathic 

Arthritis, JIA) and Annet van Royen, MD, PhD (Juvenile Dermatomyositis). 

Together, we have a longstanding track record of studying 

chronic inflammatory disorders in children. 

bvastert@umcutrecht 

Bas Vastert, MD, 


rheuma-tologist with 

expertise in translational 

immunology. He’s 

passionate about 

developing novel, 

biologically informed 

therapeutic strategies 

to personalize the 

treatment for juvenile 

idiopathic arthritis. 

This truly translational research collaboration, where basic immunological scientists and clinician 

scientists work together, lies at the heart of the acknowledgement of our department as a EULAR 

Center of Excellence in pediatric rheumatology – we’re only the 2nd pediatric rheumatology 

center worldwide. And thanks to the efforts of Nico, who has led several European Union funded 

collaborations including Pharmachild (European Pharmacovigilance register) and SHARE 

(developing evidence and consensus based guidelines on rare pediatric rheumatic diseases), 

our ability to have a real impact on patient care is excellent. 

Juvenile Idiopathic Arthritis (JIA) 

We cover a broad spectrum of chronic inflammatory diseases in children, with a particular interest 

in JIA, a chronic autoimmune disease characterized by arthritis and clinical presentation of 

systemic inflammation. In addition, we’re focused on finding off-label uses for existing drugs or 

alternative combinations of drugs in order to improve treatment strategies, and we perform 

clinical trials based on the fundamental research we perform in our labs. 

In 2014, we reported the first prospective cohort study of a first-line therapy with recombinant 

IL-1Ra in children with new-onset JIA; the majority of patients responded quickly and could stop 

treatment within one year. Based on research in our department, we postulate that timing of 

recombinant IL-1Ra administration could be change disease progression. Since then, we’ve 

initiated a the Early Stop of targeted Treatment in Systemic JIA (ESTIS), a ZonMw Rational 

Pharmacotherapy-sponsored clinical trial, where we’re testing IL-18 as a therapy response 

biomarker in systemic JIA in a multicenter clinical trial in the Netherlands. 

Another example of off-label use is nicotinamide, also known as vitamin B3, which is used as a 

dietary supplement and to treat acne and skin cancers. Most recently, we’ve planned a study to test 

whether nicotinamide can act as a regulatory T-cell-inducing compound in a stop strategy of 

biologicals and/or methotrexate (a chemotherapeutic agent and immune system suppressant), 

which are used as maintenance treatments in non-systemic JIA. 

From an immunology perspective 

We’re also understanding epigenetic and epitranscriptomic regulatory mechanisms that modulate 

immune homeostasis and might be dysregulated in chronic inflammatory (autoimmune) diseases 

like JIA. We’re using JIA as a model to study fundamental immune-regulatory mechanisms, and 

by combining our findings and observations from both the lab and the clinic, we can gain 

insight into the complex interplay between the molecules and pathways involved in 

pediatric inflammatory conditions. 

We also focus on juvenile dermatomyositis (JDM) from an immunological point of view, where we’re 

identifying distinctive and overlapping molecular mechanisms in order to develop early precision 

treatment approaches. Together Annet and Femke, have discovered and validated a novel robust 

jloosdre@umcutrecht.nl 

Jorg van Loosdregt, 

PhD is a fundamental 

immunologist who 

aims to translate 

fundamental discoveries 

into novel 

therapeutic strategies. 

He loves collaborating 

with experts in other 

fields of research. 



 

Here in the city of Utrecht, we work together with all 

kinds of organizations to ensure that children who 

want to exercise within their means enjoy sports. 

And that children coming from the hospital can work 

out at a sports club nearby. We do this with partner 

organizations in the ‘Sport op Maat’-network and the 

Wilhelmina Children's Hospital. 

- Victor Everhardt, counciler of Utrecht 

 

Translational immunology 

is much 

more than a linear 

process; it’s based 

on perpetuating 

circles of knowledge 

and implementation, 

fueled by different 

disciplines. 

- Femke van Wijk 

fwijk@umcutrecht.nl 

Femke van Wijk, 

MD, PhD focuses on 

the role of T cells in 

(tissue) homeostasis 

and chronic inflammation. 

She enjoys 

training and mentoring 

young scientists. 

marker for disease activity in JDM that can guide precision treatment; this is now being tested 

in a large international multicenter setting. In other studies. Femke has also contributed to the 

understanding of immune regulation in JIA, by proposing the paradigm of human T-cell 

resistance to regulation. Together with the pediatric rheumatology research group, she’s 

recently described a role for regulatory T-cell programming in JIA joint inflammation. 

Surprisingly, this regulatory T-cell signature is not only present in JIA and rheumatoid arthritis, 

but also in tumors, demonstrating conservation of developmental pathways across different 

diseases. 

The close-knit interaction of our team members, together with our breadth of expertise, allows 

us to expand our current understanding of the intricate mechanisms that facilitate inflammation 

in the joints of JIA patients. As translational scientists, we rely on both clinical and lab 

observations to ask the right questions and design smart experimental and clinical studies. 

Our ultimate aim is to identify novel therapeutic targets for the treatment of this disease. 


POST-ONCOLOGY 

Improving care for 

oncology PICU patients 

Marry van den 

Heuvel-Eibrink MD, 

PhD Pediatric Oncologist 

focuses on renal 

tumors and (genetic) 

variation of toxicity in 

childhood cancer. 

Roelie Wösten-van 

Asperen MD, PhD is 

a pediatric intensivist 

whose research focuses 

on pediatric cancer 

patients admitted to 

PICU. She is the chair of 

the PICU Oncology Kids 

in Europe Research 

group (POKER) 

rasperen@umcutrecht.nl m.m.vandenheuvel-eibrink@prinsesmaximacentrum.nl 

Survival rates for children with 

cancer have improved over the past 

20 years; however, intensified 

concomitant treatment has resulted 

in the fact that 40% of patients 

require at least one pediatric 

intensive care unit (PICU) admission 

throughout their disease course, 

and PICU mortality rates are higher 

(around 30%) compared to those of 

other PICU subcohorts. In addition, 

PICU mortality has remained 

relatively unchanged over the past 

decades, in contrast to the researchled 

improvements observed in 

adults with cancer admitted to 

intensive care unit. 

Identifying critically ill pediatric cancer 

patients. It’s crucial to timely identify critically 

ill hospitalized cancer patients in order to 

prevent further clinical deterioration by 

providing early-required treatment. In this 

high-risk population, we need tools that 

differentiate early between ‘relatively well’ 

and ‘critically ill’ patients (requiring PICU 

admission). We’ve launched an interdisciplinary 

research project between the PICU, 

Wilhelmina Children’s Hospital and the 

Princess Máxima Center, which aims to 

determine the predictive value of the 

Bedside Pediatric Early Warning Score 

(BedsidePEWS) for the identification of 

 

PICU mortality rates of 

pediatric cancer patients 

are far higher when 

compared to current 

mortality rates of the 

general PICU population. 

- Roelie Wösten-van Asperen 

critically ill pediatric cancer patients and, if 

necessary, to optimize the score for its use in 

this specific patient population. This will 

facilitate timely identification, referral to and 

treatment at the PICU and result in improved 

survival and reduced morbidity. 

PICU Oncology Kids in Europe Research 

group (POKER) There is little to no data on 

changes in clinical conditions in pediatric 

cancer patients preceding PICU admission; 

there is also no outcome data available. More 

research is needed to improve our ability to 

timely recognize clinical deterioration and to 

appropriately treat our patients. Recognizing 

the need for international collaboration on 

this issue, we established the PICU Oncology 

Kids in Europe Research group (POKER), 

comprising of 10 PICUs which belong to large 

pediatric oncological centers in seven 

different countries (the Netherlands, 

Belgium, Denmark, Germany, Switzerland, 

United Kingdom and France), and is endorsed 

by the European Society for Pediatric and 

Neonatal Intensive Care. As a first step, 

POKER aims to obtain consensus in 

determining the top research and core 

outcome priorities for pediatric cancer 

patients in a PICU for the next 10 years. 

Our mission in 

pediatric oncology 

research is to 

improve cure rates 

for all children and 

to enhance quality 

of survival. 

- Marry van den Heuvel-Eibrink 


POST-ONCOLOGY 

The endocrine 

system and cancer 

Hanneke van 

Santen, MD PhD 

is a pediatric endocrinologist 

with a focus on 

damaged endocrine 

systems in children. 

Endocrine effects of 

cancer treatment in 

childhood, thyroid 

tumors and craniopharyngioma. 

In 2013, she moved to 

Utrecht to support the 

new Princes Máxima 

initiative and coordinate 

endocrine care for 

children with cancer. 

hsanten@umcutrecht.nl 

It’s estimated that about 80% of pediatric 

cancer survivors reach the 5-year mark; 

however, about 50% of all patients 

experience an endocrine adverse event. 

Endocrine disorders in children with cancer 

can be caused by the tumor itself or by 

treatment. Children need an intact endocrine 

system for normal growth and to recover 

from their treatment. With early detection, 

endocrine disorders can be treated, and the 

balance or deficiency restored. 

Unfortunately, these disorders aren’t always 

diagnosed in time because they aren’t 

recognized or understood and ultimately, we 

must also find ways to prevent endocrine 

damage. 

I focus on early and late endocrine effects of 

childhood cancer treatment with a special 

interest in the thyroid and pituitary gland, 

and at improving care for children with 

thyroid cancer and craniopharyngioma. 

Rare tumors and hormonal changes 

Located in the brain, the hypothalamus and 

the pituitary gland are the main regulators of 

the endocrine system. If damaged, children 

present with a variety of clinical signs caused 

by hormonal deficiencies, including small 

stature, delay of puberty, tiredness, disturbed 

day-night rhythm, temperature instability 

and hypothalamic obesity. 

Tumors in this area during childhood are rare, 

necessitating centralization of care and an 

experienced multi-disciplinary team to 

ensure optimal treatment and outcome. 

I also study hormonal disorders during 

cancer treatment, which is challenging 

because hormones may be altered because 

of drug toxicity or because a child is ill 

(adaptive regulatory mechanism). The first 

requires hormone replacement therapy, 

while the second does not. To date, no 

prospective studies have been performed in 

children with cancer to differentiate between 

hormonal changes during childhood cancer 

and adaptive hormonal changes. 

THYRO-Dynamics Study 

We’re supported by the Foundation KIKA 

(Children Cancer-free Foundation, for The 

THYRO-Dynamics study, where we will 

prospectively measure thyroid hormones in 

children treated at the Princess Máxima 

Center (PMC). We will gain insight into the 

prevalence and causes of true thyroid 

dysfunction versus changes regarded as 

adaptation. Our findings will lead to better 

diagnostics, earlier treatment and better 

outcome for children during and after 

treatment. This new study illustrates the 

unique collaboration between the 

Wilhelmina Children’s Hospital and the 

Prinses Máxima Center. 

 

All children with (chronic) 

diseases, deserve screening and 

timely treatment of endocrine 

deficiencies, so they can grow 

and develop just as their peers. 

- Hanneke van Santen 


STRATEGIC THEMES: LIFECYCLE 

The life-course approach 

eputte@umcutrecht.nl 

Elise van de Putte, 

MD, PhD is a pediatrician 

specialized in 

social pediatrics and a 

Professor of Lifecycle 

Pediatrics. Her 

research is focused on 

well-being, participation 

and social inclusion 

in chronically ill 

children. 

The Child Health Program can be characterized by a unique life-course approach for our 

different patient groups. Our aim is to enable chronically ill children to develop and realize 

their potential. We support them in adaptation and self-management to meet the social, 

physical and emotional challenges they may encounter. A child with a chronic disease 

experiences the cumulative impact of all these challenges over time, with direct effect on 

his or her health and development. We operationalize this approach within Social Pediatrics 

Department in the PROactive life-course cohort study. 

PROactive life-course cohort study 

In this study, we collect data from young chronic patients (2-25 years old) and their parents using a 

comprehensive set of questionnaires. The aim of this research project is to study the relationship 

between chronic disease and fatigue, pain, societal participation and wellbeing – assessed from both a 

child’s and parent’s perspective. Specifically, the project aims to unravel the complex interplay of 

protective and risk factors that affect the development of these chronic patients, their societal 

participation and their wellbeing. Modern digital tools enable us to report these factors on both the 

individual and group level. 

Most pediatric patient groups participate in this life-course cohort study: patients with severe 

inflammatory disorders (juvenile idiopathic arthritis, cystic fibrosis, irritable bowel disease), children 

after oncology treatment and patients with congenital diseases (kidney, heart). A particular strength of 

this study is the integration of biological, psychological, social and behavioral data with a focus on 

well-being, including health, social inclusion and participation, and with fatigue and chronic pain as 

important proxies for these outcome measures. Clinical data are collected from the electronic patient 

file in the research data platform and are combined with the data from questionnaires that are filled 

out using a web-portal (www.hetklikt.nu). Since 2017, we’ve already included 1000 children and we 

expect to double this number by the end of 2019. 

 

The availability and cross-linking with large scale cohort studies outside the hospital, such as the 

Whistler, Piama and Youth cohorts, enable us to further understand the cumulative impact of the 

challenges that chronically ill children encounter. 

Investing in the child creates a 

threefold gain: in their present, in 

their future as adults and in their 

children, our next generation. 

- Elise van de Putte 



Let’s try to 

help patients 

manage their 

own disease. 

- Jaap van Laar 

 

Jaap van Laar, MD, PhD is an 

academic rheumatologist, and his 

professional goal has always been to 

explore new roads to improve patient 

care. He was PI of the landmark ASTIStrial 

and currently runs a productive 

research program that focuses on 

developing innovative therapies for 

systemic sclerosis and rheumatoid 

arthritis. 

jlaar@umcutrecht.nl 

Nico Wulffraat, MD, PhD is a 

pediatric immunologist and 

rheumatologist who works on JIA 

and stem cell transplantation. He leads 

studies on autologous stem cell 

transplant in JIA, vaccination 

development and drug treatment trials. 

nwulffra@umcutrecht.nl 

Pediatric and adult 

rheumatology: 

2 sides of the same coin 

Whilst the outcomes of young adults with rheumatic diseases such as juvenile idiopathic arthritis (JIA) has 

markedly improved since the introduction of biologicals and more intensive treatment regimens, they still face 

multiple challenges in daily life. Not only do they need to develop strategies to cope with pain, fatigue and 

disability, they also need to prepare for an uncertain future in terms of jobs, relationships and long-term 

outcome of their condition. Surprisingly few studies have addressed long-term multidomain outcomes in JIA 

and there is a pressing need for new observational studies of JIA patients, even those with optimally controlled 

disease. There is even less data available for patients with connective tissue diseases and immunodeficiencies. 

Basic fundamental questions remain unanswered. How is the immune system shaped by recurrent bouts of 

rheumatic disease and infections and what are the long-term clinical sequelae? 

Reuma2Go: managing disease smartly 

The successful conduct of long-term studies on 

pharmacovigilance and immune health not only requires 

smooth transitional care from pediatric rheumatology to adult 

rheumatology, but also harmonisation of data collection, 

integration of electronic patient records and development of 

tailor-made solutions (such as the use of smart mobile apps). 

We are currently setting up a prolonged transition of care plan 

supported by an E-Health tool called Reuma2Go. It is our 

ambition to promote self-management. With adequate selfassessment, 

patients can, for instance, reduce the number of 

outpatient visits when in remission. 

Predicting treatment response 

Even more relevant is the search for biomarkers predicting 

response to medication and long-term prognosis. For this we 

have set up a multicenter program (a multi “omics” approach) 

in which all Canadian and Dutch academic pediatric 

rheumatology centers participate. Patient engagement is 

critical for the successful implementation of such ambitious 

projects. Ultimately new digital technologies and advances in 

disease monitoring should help put patients in the driver’s seat 

with respect to managing their own disease. 


Transitioning care as 

child becomes adult 

Cystic Fibrosis (CF) is the most prevalent hereditary disease in 

Western countries. CF was first described just before World War 

II. At that time, all patients died during early childhood because 

of severe lung damage as a result of untreatable airway 

infections. Until the 1970s, CF was mainly a pediatric disease 

which required intensive treatment with antibiotics, chest 

physiotherapy and food supplements. With improvement of 

prognosis, new complications emerged: About one third of 

patients developed CF-related liver disease during late childhood 

and more than half acquired CF-related diabetes in early 

adulthood. Of those born in the 1980s, about 75% survived into 

adulthood. In addition to the increasing complexity of patient 

care, CF was no longer only a pediatric disease, as it permeated 

into the fields of adult lung specialists, gastro-enterologists and 

endocrinologists. Current mean life expectancy has risen up to 

almost 50 years of age and thus, care issues like male infertility, 

child birth and labor participation are reality for most patients. 

With the recent introduction of modulators of the CF 

Transmembrane Conductance Regulator (CFTR) protein, survival 

will further improve for many patients. 

Care needs to include the transition from child to adulthood 

The transition from a monodisciplinary deadly disease in children 

to a multidisciplinary complex chronic disease in older adults 

requires far-reaching changes in health care systems. For many 

years, ‘transition programs’ were developed to bridge the gaps 

between pediatric and adult knowledge and culture of care, but 

they were hampered by logistical and financial barriers. Such 

programs have never been successful and evaluations show that 

patients are dissatisfied and lost in follow-up. Transition 

programs focus on adapting the patient to the existing health 

care system, without considering changing care needs and 

prognosis. In addition, the current system impedes further 

knowledge development and innovation because ‘early 

determinants’ in childhood are disconnected from ‘late 

outcomes’ in adulthood. 

Our solution 

This is why, for years, the CF Center Utrecht has been using the 

concept of life-course care. Children and adults are followed and 

treated within a single team working with one continuous 

patient file and database, and where research focuses on 

improving the entire life-course perspective. This concept is 

accomplishing what the transition programs failed to do. 


hheijer2@umcutrecht.nl 

Kors van der Ent, MD, 

PhD initiated the Cystic 

Fibrosis Center Utrecht in 

1997 and is a co-developer 

of the Utrecht organoid 

model for CF. Kors is the 

coordinator of the European 

Union Horizon 2020 HIT-CF 

Program and the core-network 

leader for CF in the 

European Reference 

Network (ERN-LUNG) 

Harry Heijerman, MD, 

PhD is adult chest physician 

who founded (1989) and 

chaired the adult CF Center 

in The Hague and is also 

founding editor of The 

Journal of Cystic Fibrosis 

and CF Research News, of 

which he is currently 

Editor-in-Chief. 



Living better with a 

clotting disorder 

In 1964, Simon van Creveld founded a special clinic for children with hemophilia, a rare 

congenital disease. Patients with hemophilia lack clotting factors VIII or IX, 

characterized by bleeding in the joints, which leads to crippling joint arthropathy in 

adulthood. During the 1960s, these patients were admitted to the hospital for months 

and received multidisciplinary care with a physiotherapist, nurse, psychologist and 

teacher. Since then, treatment has improved and the Van Creveldkliniek has evolved 

into an outpatient clinic for patients of all ages with congenital clotting disorders. It’s 

now part of the UMC Utrecht, but maintains its unique concept of multidisciplinary care 

provided by a designated team. We provide care for approximately 50% of all patients 

with congenital clotting disorders in the Netherlands. 

rschutge@umcutrecht.nl 

kfische2@umcutrecht.nl 

Roger Schutgens, MD, PhD is an adult 

hematologist and epidemiologist. He is 

Head of the Van Creveldkliniek, Center for 

Benign Hematology, Thrombosis and 

Hemostasis. He is Chair of the 

Anticoagulation Committee at the 

UMC Utrecht, Secretary of the Dutch 

Society of Hemophilia Treaters and 

Secretary of the Dutch Society for 

Thrombosis and Hemostasis. 

Kathelijn Fischer, MD, PhD is a 

pediatric hematologist and clinical 

epidemiologist. At the Van Creveldkliniek 

(part of the UMC Utrecht), she combines 

clinical care for children with clotting 

disorders with multidisciplinary research. 

Concomitantly, she is the epidemiologist 

for two European Hemophilia Registries 

(EUHASS and PedNet) and section editor 

for ‘Thrombosis and Haemostasis’. 

Collecting interdisciplinary data 

Our research focuses on patients with hemophilia, where care and research 

are combined: All patients with severe hemophilia are seen annually within 

our multidisciplinary clinic, and their medical file includes documen tation 

of treatment and bleeds, laboratory tests, physical assess ment, 

questionnaires about physical activities and quality of life, and consultation 

with a hemophilia nurse and social worker. Provision of lifelong care 

provides the opportunity to see the effects of pediatric treatment through 

to adulthood and provides crosstalk between adult and pediatric specialists. 

Data from patient medical files, available since the 1970s, combined with 

annual multi disciplinary assessment, have established a longitudinal cohort 

study with repeated outcome assessments. 

Over the years, we’ve used these data to research effective replacement 

therapy, to understand the natural history of hepatitis C infections, to 

conduct a prospective study on cardiovascular disease and to investigate 

the value of various imaging techniques. 

Can patients with clotting disorders do sports? 

One current research project is a prospective study on sports participation 

and injuries. We started this because many patients are discouraged from 

participating in sports, because of perceived bleeding risk. At baseline, we 

test strength, endurance and coordination. Then sports participation and 

injuries are assessed for a year. The rate of injuries will be compared to 

general population data and we will use results of baseline tests to counsel 

patients on injury risk in a sports outpatient clinic. 

Our research projects strive to improve lifelong multidisciplinary care 

for patients with hemophilia and other clotting disorders. 


STRATEGIC THEMES: INTERDISCIPLINARITY 

Janjaap 

van der Net, 


physiotherapist and 

clinical health scientist, 

whose special interest is 

motor-proficiency and 

physical literacy in 

childhood chronic 

conditions. 

Tim Takken, PhD is 

medical physiologist 

and a special interest in 

clinical pediatric 

exercise physiology. 

t.takken@umcutrecht.nl 

jnet@umcutrecht.nl 

Become competent now, 

to be confident later 

A family-centered and interdisciplinary showcase for Child Health research 

At the Center for Child Development, Exercise and Physical 

Literacy, we study Activity & Health in Childhood Chronic 

Conditions. This is done in close collaboration with the 

Psychosocial Depart ment of the Wilhelmina Children’s Hospital, 

which focuses on Empowerment and Resilience in Childhood 

Chronic Conditions. Embedded within the Child Health 

Program is this complementary, interdisciplinary approach to 

studying health in childhood chronic conditions from a social, 

behavioral and physical activity perspective. 

Studying health within the context of disease 

An inspiring example is the Congenital Heart Disease-Lifespan 

study (CHD-Ls), a program in which health, rather than disease 

alone, in children with a congenital heart disease (CHD) and 

their families is longitudinally studied from as early as 20 weeks 

of gestation into their 40s. we focus on a family-centered and 

patient-centered perspective and on the physical, cognitive 

and emotional development and health in children with CHD 

and their family members. 

Nested within the CHD-Ls study is the CRUCIAL TRIAL, a 

collaboration between obstetrics, pediatric cardiology and 

cardiosurgery, neonatal and pediatric intensive care medicine, 

as well as pediatric physiotherapy, exercise physiology and 

pediatric psychology. This trial aims to minimize cerebral 

damage and increase cardiac health during pregnancy, 

perinatally and in early childhood to improve neuro-cognitive 

and motor-development as well as long-term health-related 

fitness in children with a congenital heart disease. 

Promoting physical activity in children with 

a chronic condition 

With survival rates increasing in childhood conditions (e.g. 

cystic fibrosis, childhood cancer and more recently, spinal 

muscular atrophy), as well as more efficient disease control (e.g. 

pediatric rheumatic conditions and hemophilia), there is an 

increasing desire from children and their families to be able to 

fully participate in an active healthy lifestyle. We therefore 

joined the Active Healthy Kids Global Alliance, together with 

Mark Tremblay, PhD, and expert in exercise science at the 

University of Ottawa, Canada, and produced the Dutch Physical 

Activity Report Card for Children and Youth. In this 

interdisciplinary and societal project, we collaborated with 

many national societal organizations and mapped health 

policies on local, municipal, provincial and national levels to 

improve active healthy living in children with a chronic 

condition. Together with the Department of Preventive 

Medicine and Youth from the municipality of Utrecht, we’re 

currently implementing a program “WKZsportief” to improve 

physical literacy, and to enhance participation in sports and 

active recreation in children with chronic conditions. Our motto 

for this approach is: become competent now, to be confident 

later. 


STRATEGIC THEMES: INTERDISCIPLINARITY 

Empowering the entire family 

Center of Excellence for Rehabilitation Medicine 

(De Hoogstraat Rehabilitation) 

Advances in medical technology, diagnosis and treatment have increased the life expectancy 

of various childhood disorders. Pediatric rehabilitation aims to optimize autonomy, selfmanagement 

and participation of children with developmental disabilities and their families. 

Our interdisciplinary program focuses on developmental trajectories, identification of children 

at risk for physical and mental health problems and interventions to mitigate those risks. 

Because families are central in the lives and development of children, we also focus on family 

empowerment. 

Patients and families are involved throughout our research process, from idea to 

implementation, and we have a strong collaboration with patient organizations, including 

Cerebral Palsy Netherlands (CP Nederland; formerly known as BOSK). A good example is our 

study on sleep, nutrition and physical activity of children with Brain Based Developmental 

Disabilities. Together with Neonatology, we’ve developed clinical care pathways to guide 

clinicians with assessment and early identification of problems in these areas, based on 

systematic data collection. We seek to understand the quantity and quality of sleep and its 

relationship with development. In partnership with parents, we’re developing a support 

program, including an instructional video and online knowledge translation resources, to 

educate and empower families so they can support the development and health of their child. 

mketela2@umcutrecht.nl 

We collaborate with 

patients and families in all 

stages of research. 

- Marjolijn Ketelaar 

 

Marjolijn Ketelaar, 

PhD focuses on the 

development of children 

with developmental 

disabilities, and 

empowerment of 

families to optimize 

autonomy and 

participation. 

Novel insights into cancer immunotherapy 

mboes@umcutrecht.nl 

Marianne Boes, 


immunodeficiencies 

and immune activation 

with a special 

interest in immune 

checkpoints and 

developing immunotherapy 

for cancer 

patients. 

Immunotherapy based on checkpoint blocking antibodies (anti CTLA4, anti PD-1) has 

revolutionized treatment for patients suffering from well-responding cancers such as 

melanoma and non-small cell lung cancer, which are tumors with acquired mutational loads. 

Neuroblastoma accounts for 15% of childhood cancer mortality, yet susceptibility to 

checkpoint blockade-based immunotherapy is not evident. Because the level of expression 

of major histocompatibility (MHC) Class-I molecules is low, neuroblastoma tumors evade a 

major immune defense strategy based on MHC-restricted cytotoxic T cells. In our opinion, 

induction of MHC-I membrane expression is prerequisite for optimal efficacy of T-cell therapy 

in neuroblastoma and should be incorporated into treatment regimens. 

My team initiated an interdisciplinary collaboration with colleagues at the Netherlands 

Cancer institute to screen for targets that upregulate MHC-I display at the neuroblastoma cell 

surface, yielding TNIP1 and N4BP1. Validation experiments in neuroblastoma revealed 

increased MHC-I antigen presentation capacity and induced recognition by neuroblastoma 

tumor-antigen specific T-cells. Supporting our findings, patients expressing high levels of 

TNIP1 and N4BP1 in neuroblastoma have lowered MHC-I tumor surface display and have 

worse survival probability. Use of these targets in therapy has the potential to augment 

current treatments in innovative ways that will improve clinical outcomes for neuroblastoma 

cancer patients. 


STRATEGIC THEMES: MENTAL & PHYSICAL HEALTH 

 

mgroote5@umcutrecht.nl 

Healthy play, better coping 

the importance of monitoring and acting on psychosocial development 

A child living with a chronic disease carries this burden, whether 

he or she is ill or well at any given time. It affects his or her everyday 

life. Chronic disease extends beyond the actual illness itself and 

has a negative impact on a child’s physical, social, emotional and 

cognitive development. Lower psychological well-being of and 

decreased social participation by chronically ill patients is 

demonstrated in conditions such as cystic fibrosis, autoimmune 

disorders, cardiac disorders, cancer and premature birth. We study 

play and focus on innovative gaming approaches as coping and 

healthy developmental tools for children with chronic conditions. 

For children, play is essential 

Play behavior is essential for the healthy development of an individual and 

hospitalization, pain, fatigue and social isolation limit opportunities to engage in 

social play. Play allows children to experiment with their behavioral and social 

repertoire and to practice physical and communication skills; it facilitates the 

development of social competence, emotional capacities, resilience, creativity and 

of problem-solving skills. Therefore, impaired play may have long-lasting 

consequences for these children as they grow up, in addition to the direct physical 

effects of their disease. Unfortunately, direct empirical evidence demonstrating 

the importance of play is lacking. 

Patient reported outcomes like fatigue and pain represent the 

struggles patients experience on a day-to-day basis. 

Martha Grootenhuis, 

PhD studied 

psychology and 

worked at the Emma 

Children’s Hospital 

from 1992-2015. 

Thereafter, she moved 

to Utrecht to become 

Principal Investigator 

in the Princess Máxima 

Center. Martha is 

founder of the 

Pediatric Psycho- 

Oncology Committee 

of the International 

Society of Pediatric 

Oncology (SIOP). 

- Sanne Nijhof 

Healthy Play, Better Coping 

We participate in a new multidisciplinary research project focused on play and 

applied games in children with chronic or life-threatening conditions: Healthy Play, 

Better Coping. In this consortium we investigate various ways to stimulate or 

modify play behavior and how to assess its effects on patient-reported outcomes. 

We hypothesize that helping children better adapt to the stress of their chronic 

condition will promote their short-and long-term cognitive, social, emotional and 

psychomotor development. To do this, we focus on preventative programs, 

applied games (games created with a specific purpose other than pure 

entertainment) and other interactive technologies, such as video games and 

virtual reality. Our network combines expertise from various collaborators, 

including several partners within Utrecht University (Dynamics of Youth theme, 

Game Research Graduate Program, Behavioral Neuroscience Department, Faculty 

of Veterinary Medicine); the Princes Máxima Center; and the Trimbos Institute for 

Mental Health. Our integrated systematic approach will help young patients better 

cope with the consequences of their illness by stimulating healthy social play and 

an overall healthy development. 

Social and emotional development of teenagers 

We investigate social and emotional development based on lifespan studies in 

young patients and their families. Sanne was involved in a randomized clinical trial 

FITNET (Fatigue In Teenagers on the interNET), which demonstrated the 

effectiveness of internet-based cognitive behavioral treatment for adolescents 

with chronic fatigue syndrome. Based on outcomes of the trial, Sanne has extended 

her experience with severe fatigue to new somatic domains, including 

snijhof@umcutrecht.nl 

Sanne Nijhof, MD, PhD 

is a pediatrician and 

clinical researcher with 

focus on social 

pediatrics and 

patient-reported 

outcomes, like fatigue 

and pain. She is driven 

by the hypothesis that 

(chronic) childhood 

diseases influence all 

aspects of a child’s life 

- not only the physical, 

but also the social, emotional, 

educational and 

economical. Sanne 

co-developed personalized 

digital tools to 

assess and treat the 

associated psychosocial 

consequences of 

chronic disease. 


STRATEGIC THEMES: MENTAL & PHYSICAL HEALTH 

Childhood 

cancer affects the 

whole family. 

Screening 

 

and 

monitoring help to 

prevent traumatic stress 

and provide timely 

interventions. 

- Martha Grootenhuis 

rheumatology, pulmonology and oncology. Together with Elise 

van de Putte, MD, PhD, she’s translated insights into tailored 

e-health interventions: FitNet-plus, a web-based portal for 

cognitive behavioral therapy; and PROfeel, a smartphone app 

where children can log their complaints in real-time. 

Martha’s group has longitudinally studied several pediatric 

populations. Her studies demonstrate, for example, that young 

adults who grow up with a childhood chronic disease achieve 

fewer milestones, or achieve them later than their peers across 

different domains (i.e. autonomy, psychosexual and social). A 

delayed social development, including limited participation in 

sports, was related to a lower quality of life in adulthood. This 

underlines the urgent need to address social development 

earlier in life. 

Together with Elise van Putte, MD, PhD, we collaborate in the 

PROactive study (Patient Reported Outcomes in Adolescents 

with Chronic/life-threatening disease and Tailored 

InterVentions in a digital Environment). PROactive enables the 

early detection of a disturbed psychosocial development and 

prompts subsequent interventions, that considers the 

perspective of both the child and his or her family, and aims to 

improve self-management and growth towards independency 

in adulthood. In particular, we have a special focus on fatigue 

and social/sports activities. 

Early interventions will empower our chronically ill patients 

and help them cope with the psychosocial effects of their 

physical condition. We expect that, through health play and 

game interventions, our patients will develop into healthy 

resilient adults. 


UNIQUE RESOURCES 

Patients cohorts 

in the child health program 

The Child Health program focusses on the longterm outcomes of patients with chronic diseases. 

Within the program an extensive number of longitudinal patient cohorts are being studied, many of 

them covering birth, pediatric and adult care. We invite you to collaborate with us and to add or use 

these cohort data for your own research. For full description of the cohorts we refer to our website: 

www.umcutrecht.nl/childhealth 

Congenital 

heart 

diseases 

Wilson 

diseases 

Progressive 

familiar 

intrahepatic 

cholestasis 

Mixed 

endocrine 

diseases 

Post cancer 

treatment 

Mixed 

metabolic 

diseases 

Pregnant 

women 

with fetal 

abnormality 

Congenital 

kidney 

diseases 

Extremely 

preterm 

infants 

Cystic Fibrosis 

Perinatal 

brain 

damage 

Juvenile 

rheumatic 

arthritis 

Syncytial 



Facilities 

& Expert Knowledge 

You can find some examples of our facilities & expert knowledge on the next 

pages. Lease check our website for lots more! www.umcutrecht.nl/childhealth 

Metabolic diagnostics 

We use an in-house developed direct infusion mass spectrometry pipeline to 

investigate the metabolome in patients’ body fluids and cells and to 

characterize model systems like cell lines, knock out mice and zebrafish. 

Validation of interesting findings is performed by targeted mass spectrometry 

by a range of dedicated platforms. This approach greatly contributes to 

diagnostics, disease-discovery and elucidation of pathogenic mechanisms. 

For more information please contact Judith Jans, jjans@umcutrecht.nl 

or Nanda Verhoeven, nverhoev@umcutrecht.nl 

Cardiac 3D imaging 

We are world leading in 3D imaging of the heart in young children. We have 

a state of the art catheterization laboratory with 3 dimensional rotational 

angiography that is able to obtain high resolution 3D images in small 

infants. Also fetal and neonatal MRI scanning of heart and brain is being 

performed. Furthermore we have a 3D printer that is able to convert any 3D 

dataset into a 3D model within 24 hours. 3D datasets and 3D prints can be 

further analyzed using our (MRI compatible) computational fluid dynamics 

lab and software. 

For more information please contact Hans Breur, hbreur@umcutrecht.nl 

Organoids 

We work with organoids from different disciplines. Sabine Fuchs’ 

laboratory participates in the RMCU (Regenerative Medicine Center 

Utrecht) in the Hubrecht Institute. Her main facility involves liver and 

intestinal organoid research, including functional assays and frontline 

gene-editing technologies. Clinically, we have a unique multidisciplinary 

standardized diagnostic/follow-up facility (Sylvia Toth Center) in the 

Wilhelmina Children’s Hospital for evaluation of diseases of unknown 

origin, or for the follow-up of novel treatment strategies. 

Jeffrey Beekmans’ laboratory focuses on 

translational research with stem cells in cystic 

fibrosis. He leads a research group that 

develops stem cell based culture and assay 

technology to model human pulmonary 

disease, and currently mostly focusses on 

(personalized) treatment of cystic fibrosis. 

For more information please contact 

Jeffrey Beekman, jbeekman@umcutrecht.nl 


Facilities 


Zebrafish model 

Creation of a zebrafish 

model, including gene 

knockout and knockin 

of variants. Zebra fish 

modeling 

(Hubrecht Institute, 

prof. Jeroen Bakkers) 

For information, please contact 

Gijs van Haaften, 

ghaaften@umcutrecht.nl 

meijkema@umcutrecht.nl 

René Eijkemans, 

MD, PhD focuses on 

clinical prediction 

models and machine 

learning in high 

dimensional data. He 

has worked in many 

clinical areas, in 

particular, in reproductive 

medicine. 

Applied big data analysis & 

machine learning 

In infants, Respiratory syncytial virus (RSV) is the 

leading cause of lower respiratory tract infections 

and is responsible for up to 80% of acute 

bronchiolitis cases. Several risk factors for 

developing severe RSV disease in infants have 

been identified. Nevertheless, this knowledge 

only allows us to predict approximately 50% of all 

severe RSV infections in young children. Currently, 

we cannot predict whether an infant will progress 

to severe disease, or clear the virus without 

extensive medical care. Consequently, many 

infants are hospitalized for observation, and a 

significant number do not progress to a severe 

disease condition. Thus, medical care for infants 

with an RSV infection could be more efficient and 

patient-tailored with accurate prediction. We 

investigated whether a genomic prognostic 

signature exists that can predict the course of 

RSV infection with high accuracy. We used early 

onset blood transcriptome profiles from 39 

hospitalized infants who were followed until 

recovery and whose level of disease severity was 

determined retrospectively. Applying support 

vector machine learning on age by sex 

standardized transcription data, an 84-gene 

signature was identified that discriminated 

hospitalized infants with eventually mild or 

moderate RSV infection from infants suffering 

from severe RSV disease with a validated AUC of 

0.971 on the experimental data. We conclude that 

this 84-gene signature may serve as the basis to 

develop a prognostic test to support clinical 

management of RSV patients, making the care for 

these patients more patient-tailored. 

We are drowning 

in information 

and starving for 

knowledge. 

- Rutherford D. Roger 

 



Understanding and 

treating chronic pain: 

Neuro-Immunology of pain 

Chronic pain affects more than 20% of the 

population and is a huge clinical and 

societal problem. Current therapies often 

fail because of their limited effectiveness, 

or because of severe side effects such as 

addition (opioids). We aim to understand 

how chronic pain develops in children and 

adults and identify potential differences 

between these groups. Our goal is to 

translate novel insights into ways to predict 

who will develop chronic pain to enable 

earlier pain treatment to prevent the 

development of chronic pain and to 

develop novel treatments. Based on 

recently identified neuro-immune 

interactions in chronic pain we have 

developed an interleukin-4 and 

interleukin-10 fusion protein of that shows 

remarkable effects in resolving pain; this is 

being further developed for clinical use. 

Why does pain persist? 

Pain normally serves as a warning sign of 

inflammation and damage that disappears 

when these conditions are resolved. 

However, pain persists even after cessation 

of inflammation or damage in many 

patients with inflammatory diseases, for 

example, children with rheumatic disease. 

The mechanisms for persisting pain are 

poorly understood. We hypothese that this 

persisting pain results from failing pain 

resolution programs caused by aberrant 

immune and nervous system interactions. 

For example, we’ve identified macrophages 

as key regulators of the resolution 

of inflammatory pain through interactions 

with sensory neurons. However, sensory 

neurons are also able to change 

macrophage function, such that 

macrophages switch to maintenance of 

chronic pain, independent of the original 

inflammation or damage. We study how 

these systems interact and contribute to 

pain. We’ve determined that various antiinflammatory 

cytokines signal to sensory 

neurons and glia cells to prevent 

development of long-lasting pain and also 

identified new pain genes such as 

FAM173b. 

Using a multidisciplinary approach 

to pain 

Pain is a multidisciplinary problem and 

therefore we work together with scientist 

from different disciplines (e.g. neuroscientists 

and immunologists) and 

clinicians (e.g. pediatric rheumatologists 

and anesthesiologists) within and outside 

(for the UMC Utrecht (as an example, see 

www.bonepain.eu). We use various 

preclinical chronic pain models including 

inflammatory, neuropathic, chemotherapy, 

visceral, diabetes, and osteoarthritis pain 

models. Moreover, we perform studies in 

relevant patient populations such as 

juvenile idiopathic arthritis and 

osteoarthritis. With our efforts, we’re 

taking the next step in outsmarting 

chronic pain. 

neijkelk@umcutrecht.nl 

Niels Eijkelkamp, 

PhD is an expert in the 

field of neuroimmunology. 

His research topics 

include understanding 

chronic pain and the 

development of novel 

therapeutic approaches. 

pain, a 

neglected Chronic 

global 

health problem, is 

not a symptom of 

disease but a 

pathologic entity 

that requires 

mechanism-based 

new and specific 

therapies. 

- Niels Eijkelkamp 

Pediatric exercise and muscle lab 

Special equipped to measure al relevant parameters of health related 

fitness, including Bio Impedance measures and nutritional status. 

Including a platform to measure real-time –Spectrometry (7T) of 

exercise metabolism and Near Infrared Spectography (NIRS) in 

muscles. 

For more information please contact Janjaap van der Net, jnet@umcutrecht.nl 

or Tim Takken, ttakken@umcutrecht.nl 


Facilities 


Functional brain measurements 

1. State-of-the-art neonatal and infant MRI scanning 

(3 tesla and recently 7 tesla) including advanced 

postprocessing (e.g. DTI, MRS, Segmentations 

(volumetric measurements)). 

2. State-of-the-art cerebral ultrasound. 

3. State-of-the-art neuromonitoring (aEEG, NIRS, 

sleep assessments). 

4. A dedicted highly specialized 

neurodevelopmental follow up group 

For more information please contact 

Jeroen Dudink, jdudink@umcutrecht.nl 

Translational research 

for early stages of life 

What happens early in life can have detrimental effects 

later on. The Department for Developmental Origins of 

Disease provides unique resources to the Child Health 

Program and we focuse on causes, consequences of and 

cures for adverse events that occur during early life stages. 

We collaborate with patient organizations and clinical 

investigators in the Neonatology, Obstetrics and Pediatric 

Departments, UMC Utrecht to ensure that we develop 

interventions that truly matter to our patients and families. 

Using cutting edge techniques and biotechnological 

innovations, in collaboration with technical universities in 

Eindhoven and Delft, we combine molecular, anatomical, 

physiological and behavioral expertise and investigate 

intra-uterine processes and interventions to prevent 

cardiovascular and neurodevelopmental disorders later in 

life (led by Titia Lely, MD, PhD); the developing connectivity 

of neuronal networks that enable social play, motor 

learning and cognition (led by Freek Hoebeek, PhD); and 

novel neuroprotective and neuroregenerative 

interventions including stem cells, nutrition and growth 

factors for perinatal brain injury (led by Cora Nijboer, PhD). 

 

Translational 

research not 

only spans 

fundamental to 

clinical science, 

but also forms 

the bridge 

allowing Child 

Health experts 

to innovate 

therapies. 

- Freek Hoebeek 

fhoebeek@umcutrecht.nl 

Freek Hoebeek, 


neuroscience and 

building multidisciplinary 

research teams. 

He is the UMC Utrecht 

Chair of Translational 

Research of Early Life 

Events in 2018. 



Clinical Trials 

Changing lives through trials 

An important aspect of research in 

pregnant women and children is the 

design and performance of clinical studies 

and trials. To do this in the best way, we’ve 

taken an approach which translates basic, 

fundamental science into clinical 

application, by developing innovative, 

patient-centric biomarkers and 

therapeutics. We also collaborate with 

public and private sectors to bring a 

spectrum of innovative treatments, not 

easily or readily available, to children in 

need. By working with scientists, clinicians, 

institutes, and industry, the sum of its parts 

is truly greater than what could be 

achieved alone. 

The UMC Utrecht U-TRIAL initiative helps 

researchers within this strategic theme 

bring their research ideas to the forefront. 

Together with patient organizations, 

health authorities, industry partners and 

Julius Clinical (the academic research 

organization spin-off of the UMC Utrecht), 

investigators are stimulated to develop 

new and impactful clinical hypotheses 

which can be tested within a bold, highquality 

framework. In doing so, we deliver 

essential clinical results and thereby 

treatments to quickly and effectively 

improve the health of pregnant women 

and children. 

cpark@umcutrecht.nl 

Cyrus Park, MSc, MBA 

Strategic Advisor – Trial 

Development U-TRIAL 

initiative to stimulate 

innovative, impactful 

clinical research to benefit 

UMC Utrecht and society. 

Clinical Trials in UMC Utrecht 

1,546 

studies 

1,335 

medical conditions 

Pediatric Clinical Trials in UMC Utrecht 

315 trials in children 

226 

interventional 

89 

observational 

169 

industry 

funded 

collaborations 

146 

other funded 

collaborations 

Source: clinicaltrials.gov 


EDUCATION AND TALENT 

Attracting and 

advancing talent 

Berent Prakken, acting dean: Child Health has a strong focus 

on education, and for a very good reason: Education holds the 

key to our future. Our education program is aimed at different 

audiences ranging from patients to health professionals and 

scientists. We specifically support targeted programs for talent 

management that help young researchers focus their efforts 

towards real and sustainable societal impact. 

 

 

Education 

holds the 

key to our 

future. 

- Berent Prakken 

 

There are no better 

teachers for 

upcoming physicians 

than patients and 

their loved ones. 

- Joost Frenkel 


EDUCATION AND TALENT 

TULIPS program 

New researchers within the Child Health 

program are actively stimulated to 

participate in the national TULIPS program 

(Training Upcoming Leaders in Pediatric 

Science), an initiative of the Dutch Society 

for Childcare. The vision of TULIPS is that 

high-quality research is required to 

improve child health. TULIPS has the 

mission to empower young clinician 

scientists to become international 

competitive researchers. Therefore, TULIPS 

provides distinct, selective 2-year curricula 

for PhD students and Postdoctoral fellows. 

Both curricula provide interactive training 

sessions and weekend educational retreats 

to create opportunities for collaboration 

and to enhance competences required to 

become successful in Pediatric Science. 

bprakken@umcutrecht.nl 

Berent Prakken, MD, PhD 

Pediatric Immunology, 

Acting Dean, Education 

Director Biomedical 

Education Center 

Summer Schools 

The Child Health program hosts several 

Summer Schools during the summer. 

These educational activities introduce 

global child health to young doctors and 

master’s students and stimulate working 

together in an international environment. 

The Summer School on translational 

medicine is organized together with 

students from the international Apollo 

Society (https://www.apollosociety.eu/) 

and hosts an impressive international 

faculty. By organizing joint events between 

summer schools, we are building a lasting 

network of young researchers. 

EUREKA Institute 

The Eureka Institute of Translational 

Medicine is the result of a close 

collaboration between the UMC Utrecht, 

various other top universities (Stanford 

University, Duke/NUS Medical School, 

University of Arizona, University of Miami, 

University College London and the 

University of Toronto), research institutions 

(TIP, Center for Translational Molecular 

Medicine), foundations (Dutch Arthritis 

Foundation) and industry (Nutricia 

Research). Nature Medicine and Nature 

Biotechnology have supported the 

program, in addition to providing learning 

materials. The Eureka Institute was initiated 

to develop an international community of 

translational medicine professionals 

equipped to catalyze the application of 

discoveries for the benefit of human 

health. The Institute offers a unique 

translational medicine course, the 

International Certificate Program and 

within this framework we’ve developed a 

special program for researchers appointed 

within Child Health. This program 

stimulates new researchers in crucial areas, 

such as teambuilding and collaboration; 

critical thinking and problem solving; 

translational medicine and valorization. In 

collaboration with the Eureka Institute, we 

also organize masterclasses with internationally 

renowned facilitators for young 

talent in Child Health. 

jfrenkel@umcutrecht.nl 

Joost Frenkel, MD, PhD 

is a pediatric rheumatologist 

with a keen interest in 

mechanisms of inflammaton. 

He is an excellent 

clinical teacher, putting 

patients and families center 

stage. Current research 

involves both patientcentered 

education and 

disorders affecting the 

innate immune system. 

 

Boost Grants 

One of the main strategic themes of the 

Child Health program is interdisciplinary 

research. To stimulate young investigators 

to share their research experiences with 

colleagues outside their own professional 

expertise, we have launched annual Boost 

Grants. Young investigators within the 

program are asked to submit research 

proposals in collaboration with one or 

more investigators in the program with 

whom they have never worked before. 

Each year, this produces 15-20 new 

research ideas that are presented and 

discussed during general Child Health 

meetings. The three best ideas are 

rewarded with an amount of 15,000 Euros 

to start the project and generate pilot data 

for future larger grant applications. 

Doctors must understand a patient’s 

perspective to establish a balanced 

relationship. This calls for novel education, 

both in the classroom and at the bedside - 

education that gives patients a voice that 

physicians hear, so they can jointly reach a 

shared decision. 

- Joost Frenkel 


Science 

for life

Child research

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