The most feared gastrointestinal disease in preterm babies is necrotizing enterocolitis. Despite advances in neonatal care, the incidence of NEC is increasing, with classical NEC occurring in approximately 5–10% of very low birth weight (VLBW) infants (i.e. birth-weight < 1500 g. ; NEC affects mainly the most preterm babies, and the course of disease is worse in these most vulnerable children. In the Netherlands this amounts to some 200 cases per year, which makes it a rare disease.
The cause of NEC is multifactorial. An immature inflammatory response, aberrant bacterial colonization of the immature gut and impaired vascularization are all involved. ; As the cause of NEC is as yet not elucidated, treatment consists of a standardized supportive regime of antibiotics and bowel rest. When there is intestinal perforation or deterioration despite maximal medical therapy, surgery is needed. Surgery is aimed at containing peritonitis and sepsis by resection of all avital intestine, followed by either primary anastomosis or creation of an ostomy.
Over the last 20 years this has not changed, and outcomes remain rather dismal. Some 40% of babies succumb during of after surgery, while up to 70% will suffer from long term sequelae including neurodevelopmental delay and gastrointestinal consequences such as short bowel syndrome.
The UMCG has been recognized by the Ministry of Health as Center of Expertise for Rare Diseases regarding Necrotizing Enterocolitis, and participates within the European Reference Network Inherited and Congenital Anomalies (ERNICA).
Our group works currently on the following multidisciplinary projects:
Our work has been embraced by the UMCG KOERS25 program as a clinical example of value based health care, and is part of the ‘Beatrix Children’s Hospital Value Gardens’. The application of artificial intelligence to moral decisions is a novel research field and results from our studies will be applicable to all kinds of morally loaded choices, both within and outside medicine. We have already established a NEC choice experiment for Dutch doctors, and are now working to extend this to parents and doctors within the European Reference Network Inherited and Congenital Anomalies (ERNICA). Similarly, parents and patient organizations are essentially involved in the development of the international Core Outcome Set. We set out to make this COS as international as possible, including high as well as middle/low income countries. This way, the COS will be applicable around the globe, both for research as well as for national and international benchmarking and the subsequent identification of best practices.
These ambitions can only be achieved via national and international multidisciplinary collaboration. We work closely together with other renowned institutions such as Great Ormond Street Hospital London, the Hospital for Sick Children in Toronto and Johns Hopkins Children’s Center in Baltimore, both on the clinical as well as the fundamental research parts. We are not only involved in ‘high tech’ fundamental studies, we are also involved in clinical and teaching projects in low and middle income countries (e.g. Tunisia, Indonesia, Curacao)
A goal for 2023 is the organization of the NoMoreNEC music festival. Originally this was supposed to be held in 2020, with several well-known Dutch musicians and bands attending. However, when COVID struck this festival had to be postponed. Hopefully we will be able to organize it in 2023, to raise both awareness and funds for one of the most dreadful diseases in preterm infants.
Clinical research performed aims to improve the outcome of babies with NEC. We are investigating several biomarkers for prediction and early detection of NEC as well as for predicting complicated NEC, defined as the need for surgery. Early identification of children who will develop NEC will enable us to deploy targeted preventive strategies. An early diagnosis of NEC will lead to an earlier start of treatment, but also the avoidance of unnecessary treatment of babies in whom NEC is suspected. Finally, the identification of those children in need for surgery might lead to improved surgical outcomes but also to a better counselling of parents.
While a lot of NEC related research is being performed, studies often are small and reported outcomes vary among studies and might not always be the most relevant to neither the scientist nor the patient/family. Therefore we are developing an international NEC Core Outcome Set following the COMET (Core Outcome Measures in Effectiveness Trials) protocol. Such a NEC COS aims to standardize the reporting of outcomes, reduce bias and facilitate meta-analyses. In addition, it will include the patient perspective, as one of the most important stakeholders.
This COS will also form the backbone of the Dutch NEC registry which we have initiated and are now working on with all Dutch neonatology centers. With such a registry we aim to increase numbers both for research as well as for benchmarking and the identification of best practices.
Our fundamental and translational research aims to broaden our knowledge of the (patho)physiology of the neonatal intestine. We focus on (the relation between) the neonatal intestinal inflammatory response, bacterial colonization and intestinal circulation. We perform and have performed several prospective and multidisciplinary studies, combining knowledge and expertise of all participants. To that end we collaborate closely with our partners from the departments of neonatology, pharmacy and pathology, as well as with international partners such as Great Ormond Street Hospital London. Such fundamental knowledge will lead to improved preventive strategies as well novel therapeutic strategies, and several of our findings have made it to the clinic or are expected to reach the clinic within a few years from now.
Finally, decision making in NEC is ethical to it’s core. We have established a working group consisting of physicians, ethicists, and specialists in the relation between artificial intelligence and human decision making to elucidate the factors underlying doctor’s and parent’s decisions to proceed to surgery or rather to divert to comfort care. We will use this technique both on a national as on an international level, investigating differences between medical specialists and centers, but also between medical specialists and parents. This knowledge will be used to develop a decision aid for doctors and parents regarding perhaps the most morally loaded decision in medicine: whether to proceed to surgery or divert to comfort care in a critically ill neonate. Our aim is to empower both patients and doctors by providing them with insight into their own thinking, as well as in that of others in similar situations, thereby improving both autonomy and shared decision making. These studies are performed in close collaboration with the TU Delft and Councyl, a private company. Of course these studies are also aligned with the Data Science Center in Health of the UMCG and have been adopted by the UMCG Value Based Health Care program.
Janneke L.M. Bruggink, pediatric surgeon, PI
Daphne Klerk, MD/PhD student
Otis van Varsseveld, MD/PhD student
Martin van der Heide, MD/PhD student
Raquel dos Santos Martins, PhD student
Prof. Dr. Arend F. Bos, neonatologist
Dr. A. Timmer, pathologist
University Medical Center Groningen (UMCG)
Department of Surgery
PO Box 30.001
9700 RB Groningen
The Netherlands
Visiting address
University Medical Center Groningen (UMCG)
Department of Surgery
Hanzeplein 1
9713 GZ Groningen
