Research overview and current projects

Below you will find a list of current research projects in The Department of Neonatology.

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Ph.D. projects

Change in gut motility in preterm Infants and Piglets 

Susanne Søndergaard Kappel, (Lise Aunsholt, Ragnhild Maastrup)
The overall aim of this thesis was to gain better insight into feeding intolerance and disturbed bowel habits in preterm infants. This is reached by detailed infant and piglet studies on how gastric residuals (GR) and gut dysmotility are associated with clinical symptoms, including NEC. 
The project includes following goals:
  • Identifying how GR measurements are used by clinical personnel in Denmark. A questionnaire was developed to find out how nurses and physicians conceptualize and describe the evaluation and decision-making for GR measurements. (accepted for publication, sep 2021)
  • Evaluate differences in gut motility between infants receiving two types of fortification. Multicenter RCT study.  Very preterm infants randomized to human milk fortified with bovine colostrum or conventional fortifier based on formula products (FM85). (submitted, dec 2021)
  • Test if gut transit time, GR volume and composition can predict NEC onset in preterm piglets. An established and validated 5-day protocol for inducing NEC in preterm pigs is used. Gut transit time and GRs are evaluated in healthy piglets and piglets with NEC in relation to diet composition and postnatal age. (published February 2020 and January 2021)
Enrolment ends 31. January 2022.

Pediatric delirium in critical care: a prospective intervention study with parental involvement

Rikke Louise Stenkjær, (Janne Weis, Gorm Greisen, Suzanne Forsyth Herling and Ingrid Egerod)
Aim: The overall aim of the study is to investigate detection, prevention and reduction of delirium in acute and critically ill children aged 3 months – 18 years of age. The specific objectives are: 
1. Investigate prevalence and duration of delirium and validate the screening tool SOS-PD  
2. Develop a non-pharmacological complex intervention to prevent pediatric delirium through an international Delphi study
3. Pilot testing of a non-pharmacologic intervention including partnership with parents to prevent or reduce pediatric delirium and investigating parents’ experiences of participating in intervention delivery
Design: Construct validity evaluation, Complex intervention development based on Delphi-study, and evaluation of intervention implementation through semi-structured interviews.
Status June 2021: Two manuscripts are in preparation, submission in Autumn 2021. 50 children out of 140 are included. 

The SafeBoosC-III follow up study

Marie Isabel Rasmussen, (Mathias Lühr Hansen, Gorm Greisen)
In the SafeBoosC-III trial, the objective is to investigate if treatment based on brain oxygenation in extremely preterm infants can improve survival and reduce the risk of brain damage. 
We know that extremely premature babies have a high risk of neurodevelopmental impairment such as brain damage as well as psychological and motor problems. This can affect both the child and the family for the rest of their lives. Therefore, we are now conducting a follow-up study where we look at the children's development when they are two years old. It is important to investigate whether the potential effect of the trial persists in early childhood, in the form of less risk of cerebral palsy, low intelligence quotient and / or other neuropsychological late effects. It is also important to investigate if there are any unexpected harms. We will use data from health care records, parent questionnaires and psychological assessments. The follow-up study will take place in more than 60 departments across 18 countries and is expected to be published in an international peer-reviewed medical journal.

PrePhage – Improving gut flora in preterm infants using beneficial viruses from healthy infants

Gustav Riemer Jakobsen (Lise Aunsholt, Susanne Søndergaard Kappel) 
The purpose of this study is to improve gut flora in preterm infants and ultimately prevent the severe gut-disease, necrotizing enterocolitis (NEC). We aim to transfer isolated viruses - so called bacteriophages - from healthy term infant stool, to preterm infants. 
The project has the following sub-goals: 
  • Mapping the development of normal gut bacteria and viruses in healthy term infants and examining the relationship between the bacteria and viruses and external factors such as diet
  • Testing the effect of human bacteriophage transfer to preterm piglets. This study will examine both the safety of the treatment, if the treatment prevents NEC, as well as examining how the treatment works
  • Testing the effect and safety of treating with gut-viruses in preterm infants for the first time worldwide. We believe that the beneficial gut viruses will have a protective effect on the preterm infant’s fragile intestinal system. 
The primary goal is to ensure that the treatment is in fact safe. If the infants who in this study receive the treatment do not experience serious side-effects, a larger study will be performed. 
This study is done in collaboration with 2 departments at the University of Copenhagen: Translational Pediatrics and Nutrition, and Microbiology and Fermentation. 

Surfactant treatment in preterm infants: improving education, assessment, and clinical outcome

Niklas Breindahl (Lise Aunsholt, Martin Tolsgaard and Tine Brink Henriksen)
The purpose of this PhD-project is to gain insight to optimize surfactant treatment using the LISA method in preterm infants with respiratory distress syndrome (RDS).
In our first study, we will conduct a Delphi-survey to achieve international consensus on the training needs to inform a simulation-based curriculum and an assessment tool designed to evaluate competence among LISA operators. Based on these results, we will develop a simulation-based education using a simulator for exploring critical aspects of LISA performance. 
In our second study, we will collect validity evidence for the assessment of LISA in a controlled training environment without any patient risks. Further, we will collect data in the simulated setting to train a model using neural networks informed by hand-motions and video from the laryngoscope obtained during the procedure. 
In our third study, we will randomize preterm patients with RDS to receive LISA either using standard pharmacological analgesic treatment or a non-pharmacological approach as there is clinical equipoise regarding the effect of pharmacological analgesic treatment when performing LISA.
This PhD-project is expected to be terminated in January 2026.


Pre-graduate projects

Methicillin-resistant staphylococcus Aureus (MRSA) outbreak in the department of Neonatology, Rigshospitalet 

Julia Galuszka (Rikke Louise Stenkjær, Lise Aunsholt)
Purpose: The purpose of the study is to establish which events during hospitalization in the NICU that might be connected to a greater risk of MRSA infection and get a greater understanding of the MRSA transmission in the department.  
Design: The study is retrospective study based on medical journals from the Department of Neonatology, Rigshospitalet, from 2019 and onward.
Status June 2021: Article in progress. Submission expected mid-2022 

Bowel habits and gastrointestinal presentation in preterm infants – an observational study

Ulrikke Lyng Beauchamp, (Susanne Søndergaard Kappel, Lise Aunsholt).
Purpose: To investigate whether an implemented observational sheet focusing on bowel habits and gastrointestinal symptoms, will affect the timing of the decision to initiate laxatives in preterm infants.
Design: Combined prospective and retrospective study. 
Status September 2021: Implementation of observational sheet to all new kids within the gestational age 24 weeks to 30+6 weeks.

How Covid-19 affected the NICU; A single-center experience. 

Caroline Kleis Schmidt (Pre-graduate student), (Lise Aunsholt, Morten Breindahl). 
Aim: The study aims to report how the COVID-19 pandemic affected the patients, the patients’ next of kin, and employees at the NICU at Rigshospitalet, Copenhagen.                            
Design: A retrospective assessment based on data collected through the Vermont Oxford Network and interviews with multiple of the department’s employees.                                                                             
Status August 2021: The paper is under preparation and will be sent for review during fall 2021.

Postdoc projects and other projects

SafeBoosC-III 

Mathias Lühr Hansen (trial manager), Gitte Holst Hahn (principal investigator GN), Gorm Greisen (coordinating investigator). 
Purpose: evaluating the benefits and harms of clinical care with access to cerebral oximetry monitoring for the first three days of life, in extremely preterm infants 
Design: Randomised clinical trial, multicentre, 71 neonatal intensive care units from 17 countries are actively recruiting
Status August 2021: 1250 participants randomised, expected completion of recruitment in January 2022

Assessment and management of pain in hospitalized infants, children and young people in Denmark

Janne Weis (national coordinator) and Ragnhild Maastrup.
Aim: To investigate health care professionals’ documented pain assessment and management, among hospitalized infants, children and young people at neonatal and pediatric units in Denmark.
Design: Audit of journals three days in November 2020 at 95% of the Danish departments for neonatal, children and young people.
Status September 2021: Article in manuscript, expected submission end 2021.

Parent-Infant Interactions among Infants at High Risk for CP: Protocol for an Observational Study of Infant and Parental Factors for Dyadic Reciprocity 

Anne-Mette Bæk Jensen, Ane Lando
Aim: To assess the quality of early parent-infant interactions in families with high-risk infants, compared to families with low-risk infants, and to explore how interaction quality is affected by infant and parental factors. Three potential mediating factors explaining the association between CP risk and less optimal parent-infant interactions will be explored: infant interactional capacities, parental mental health and wellbeing, and parents’ representations of their child. 
Project period: 2020 - 2029

Detection of EEGrafic seizures by neonatologists using 2-channel monitors. Intra- and interrater agreement

Gitte Holst Hahn, Anne Mette Plomgaard, Christian Heiring, Melita Cacic and Gorm Greisen
Background: Seizures are common in newborn infants and in order to guide anticonvulsive treatment continuous EEG-monitoring of infants with high risk of seizures, or with clinical symptoms that are compatible with seizures has become standard practice in neonatal intensive care.
Purpose: The purpose of this study is to quantify the intra- and interrater agreement among a rather large group of neonatologists with varying experience in aEEG/EEG monitoring.
Design: Retrospective study on already obtained aEEG/EEG data from 90 mature neonatal infants with regard to seizure burden and background activity.
Status: winter 2021-22: rating of aEEG, fall 2022: data analyses and writing the manuscriptfall

Constipation in Premature Infants – A Survey about the Practice in Danish Neonatal Departments

Rasmus Kolind, Susanne Søndergaard Kappel og Lise Aunsholt
Aim: To investigate the understanding and management of constipation in premature infants in Danish Neonatal units. 
Design: A survey sent to all nurses and doctors at Danish Neonatal units treating infants with gestational age < 32 weeks.
Status September 2021: Article in progress. 

Fast assessment of surfactant deficiency (FAST Trial) 

Christian Heiring, Porntiva Poorisrisak, Peter Schousboe, Henrik Verder
Aim: to use a test of lung maturity by measuring surfactant levels right after birth of a premature baby to determine the need for treatment with exogeneous surfactant in order to allow for targeted and faster treatment of only those infants showing low surfactant levels
Method: randomized clinical trial in 4 danish university based neonatal units
Status: awaiting approval from VEK

ONE study 

Christian Heiring, Lise Aunsholt
Aim: to determine the optimal route for neonatal intubation in an acute situation
Method: Benchtop study using with a simulated neonatal resuscitation measuring different speed and accuracy of different providers performing oral or nasal intubation on a manikin.
Status: protocol phase​

O2Matic 

Christian Heiring
Aim: to assess a device for automatic oxygen control in preterm infants receiving high flow therapy (HFT) as respiratory support
Method: randomized cross over design in a group of preterm infants on high flow therapy. The patients will cross over from receiving HFT with standard nurse driven regulation of inspired oxygen level to automatic regulation of inspired oxygen level using a device called O2Matic and vice versa, measuring the duration of the  blood oxygen level measured by pulse oximetry being within the prescribed range.
status: protocol phase, ready for seeking VEK approval

Single-family rooms (SFR) in a Neonatal Intensive Care Nunit (NICU): A Thematic analyses of experiences from parents and nurses. 

Joan Neergaard Larsen
Background and aims: Due to damage by water we had to move to a temporally satellite unit, with SFR instead of two-bedded rooms. The situation constituted a window of investigation to collect experiences from parents and nurses related to SFR.
Method: We conducted two focus group interviews: The first one included six parents. The second included five nurses. Before the interviews, the participants were provided with a set of unfinished sentences which they completed in writing as self-reflection in preparation for the interview. The unfinished sentences were developed to target each focus group and were inspired by Guided self-determination (GSD) an evidence-based method and a dialogue tool for mutual decision making. The interviews were analyzed using thematic analysis. Ethical approval was obtained, and the all participants gave informed consent.
Status March 2022: Article in progress, submission expected fall 2022.

SUGARNIRS

Sandra Meinich Juhl, Gitte Holst Hahn, Gorm Greisen Gitte Zachariassen, Henrik Christesen, and Pernille Langkjær Gormsen
Aim: To determine with near-infrared spectroscopy the glucose threshold for unchanged cerebral oxygenation after rescue therapy for hypoglycemia in term or near-term neonates.
Design: We plan to study the effect on cerebral oxygenation of an intravenous glucose bolus in two groups of infants 1)30  hypoglycemic infants who are treated according to the national guideline for hypoglycemia and 2) 30 infants who receive an intravenous access to receive antibiotics. The study will take place at Rigshospitalet in Copenhagen (RH) and H.C. Andersen’s Hospital in Odense (OUH).
Status: Project submitted to ethical committee.​

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