Henrik Holmstrøm

• Vallevik, Elin Ørbeck; Holten-Andersen, Mads Nikolaj; Carlsen, Karin Cecilie Lødrup; Skjerven, Håvard Ove; Vettukattil, Riyas & Rueegg, Corina Silvia [Show all 14 contributors for this article] (2026). Oscillometric blood pressure values in infants at 3, 6 and 12 months of age: a cohort study. BMJ Paediatrics Open. 10(1). doi: 10.1136/bmjpo-2026-004761. Full text in Research Archive
• Klungerbo, Vibeke; Døhlen, Gaute; Holmstrøm, Henrik; Edvardsen, Elisabeth; Matthews, Norunn Iren Lindbak & Möller, Thomas (2026). What Limits Cardiorespiratory Fitness in Adolescents with Fontan Circulation: An Integrated Hemodynamic and Pulmonary Perspective. Pediatric Cardiology. ISSN 0172-0643. doi: 10.1007/s00246-026-04231-1. Full text in Research Archive Show summary

  Cardiorespiratory fitness (CRF) is strongly associated with morbidity and mortality in patients with Fontan circulation. However, the factors influencing CRF during adolescence remain incompletely understood. The primary aim of this study was to investigate the associations between CRF and ventricular function represented by end-diastolic pressure (VEDP), the transpulmonary pressure gradient (TPG), somatic growth (height) and pulmonary diffusing capacity (DLCO/VA). The secondary aim was to assess the prevalence of exercise oscillatory ventilation (EOV) and its physiological associations. In this national, cross-sectional study, 44 adolescents (median age 16.6 years) with Fontan circulation underwent cardiopulmonary exercise testing, heart catheterization and pulmonary function assessment. Peak oxygen uptake (V̇O₂peak) was modelled as the dependent variable in a multiple linear regression with VEDP, TPG, height, and DLCO/VA as predictors. Logistic regression was used to identify physiological associations of EOV. The multiple regression model for absolute V̇O₂peak explained 61% of the overall variance. Lower VEDP and greater height were independently associated with higher V̇O₂peak. When V̇O₂peak was expressed relative to body mass, TPG also became associated with higher V̇O₂peak, while greater height and lower VEDP remained associated. This model explained 30% of the variance. DLCO/VA was not independently associated with V̇O₂peak. EOV was observed in 50% of patients but showed no association with V̇O₂peak, hemodynamic, or pulmonary variables. In adolescents with Fontan circulation, lower resting VEDP and somatic growth were associated with higher CRF, reflecting more efficient hemodynamics. Pulmonary diffusing impairment and EOV were common but not significantly associated with lower CRF.

• Malekzadeh-Milani, Sophie; Padovani, Paul; Sivakumar, Kothandam; Goronflot, Thomas; Méot, Mathilde & Jones, Matthew I. [Show all 59 contributors for this article] (2025). Outcomes of transcatheter patent ductus arteriosus closure in infants weighing 2 to 6 kg. Revista Española de Cardiología. ISSN 0300-8932. p. 1–13. doi: 10.1016/j.recesp.2025.09.005. Full text in Research Archive
• Klungerbo, Vibeke; Hirth, Asle; Fredriksen, Per Morten; Holst, Rene; Edvardsen, Elisabeth & Holmstrøm, Henrik [Show all 7 contributors for this article] (2025). Reference models for individualized assessment of cardiorespiratory fitness in children and adolescents with congenital heart disease: a retrospective multicentre study. European Journal of Pediatrics. ISSN 0340-6199. 184. doi: 10.1007/s00431-025-06270-x. Full text in Research Archive Show summary

  Cardiopulmonary Exercise Testing (CPET) is considered the gold standard assessment of peak oxygen uptake (peak), and consequently, cardiorespiratory fitness (CRF). Common practice in children with congenital heart diseases (CHD) is to compare individual test results to reference values in healthy children. This approach does not account for the diversity of heart defects and may also be demotivating for children with CHD. This retrospective multicentre study aimed to establish individualized CRF reference models specific to children with CHD, to facilitate a better understanding and management of their condition. A total of 1475 CPETs until exhaustion were performed in 943 children and adolescents at two hospitals in Norway. The children and adolescents were categorized into three groups: simple defects (VSD, ASD, CoA, LVOTO; n = 497, 38% female), moderate defects (TGA, Fallot; n = 299, 41% female), and univentricular defects with a Fontan circulation (n = 147, 42% female). Multivariable mixed-effects models with individuals as random intercepts were used to develop group-specific reference models for CRF. Estimated predictive models including covariance matrices for each group and outcome are provided, allowing for the generation of reference values with confidence intervals for clinical and research applications. Conclusion: Treadmill-based reference models for maximal and submaximal CRF variables in the most prevalent types of CHD are presented. Using individualized reference values has the potential to improve clinical decision-making for children with CHD and to enhance their sense of mastery. A web-based calculator is available for quick and easy clinical use.

• Diab, Simone; Rösner, Assami; Døhlen, Gaute; Brun, Henrik; Grindheim, Guro & Vithessonthi, Kanyalak [Show all 9 contributors for this article] (2025). Systolic Function in the Fontan Circulation Is Exercise, but Not Preload, Recruitable. Journal of the American Society of Echocardiography. ISSN 0894-7317. 38(4), p. 342–352. doi: 10.1016/j.echo.2024.11.005. Full text in Research Archive Show summary

  Background - Fontan circulatory failure with impaired systolic function is well documented; however, its mechanisms are not fully understood. The aim of this study was to explore myocardial functional reserve in adolescent patients with Fontan circulation in response to exercise or acute preload increase.<p> <p>Methods - The study included 32 patients (median age, 16.7 years; range, 15.4–17.9 years; 12 female patients) with Fontan circulation. Echocardiographic imaging was performed during exercise using a recumbent cycle ergometer and during heart catheterization with a rapid infusion of 0.9% saline infusion at 5 mL/kg body weight. Myocardial peak longitudinal strain (LS) was measured in a four-chamber view during specific time intervals before, during, and after exercise (LS_stress) and volume load (LS_cath). During catheterization, central venous pressure and ventricular end-diastolic pressure were simultaneously recorded. A control group of 16 healthy individuals participated in the exercise test.<p> <p>Results - Mean LS_stress was less negative for patients than for control subjects (P ≤ .001 at all stages); however, it significantly improved from −18.4 ± 5.5% at baseline to −22.0 ± 6.5% (P = .004) at maximal loading. LS_stress at maximal loading did not correlate with changes in heart rate. During catheterization, mean LS_cath was −19.6 ± 6.0% at baseline and did not improve significantly at 1.00 to 2.00 minutes and at 4.00 to 6.00 minutes after saline infusion. In more than half of the patients, LS_cath worsened or improved by less than −2% after saline infusion. Worsening of LS_cath correlated with central venous pressure and ventricular end-diastolic pressure in all conditions (P ≤ .017). There was no difference in LS_stress or LS_cath between the morphologic right ventricle and the morphologic left ventricle.<p> <p>Conclusions - Patients with Fontan circulation demonstrate systolic myocardial functional reserve that can be recruited with exercise stress but not with an acute increase in preload.

• Hjorth-Johansen, Elin; Børøsund, Elin; Moen, Anne; Martinsen, Ingeborg; Wik, Gunnar & Solevåg, Anne Lee [Show all 8 contributors for this article] (2024). An individualised mobile app was beneficial for the mothers of infants with severe congenital heart defects. Acta Paediatrica. ISSN 0803-5253. 114(6), p. 1238–1248. doi: 10.1111/apa.17556. Full text in Research Archive
• Nordklev, Cecilie Bryn; Gjesdal, Ola; Gunnes, Nina; Holmstrøm, Henrik; Morken, Nils-Halvdan & Vangen, Siri [Show all 7 contributors for this article] (2024). Down syndrome and associated atrioventricular septal defects in a nationwide Norwegian cohort: Prevalence, time trends, and outcomes. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 103(10), p. 2024–2030. doi: 10.1111/aogs.14932. Full text in Research Archive Show summary

  Introduction The prevalence of Down syndrome (DS) is approximately 1 per 1000 births and is influenced by increasing maternal age over the last few decades. DS is strongly associated with congenital heart defects (CHDs), especially atrioventricular septal defect (AVSD). Our objectives were to investigate the prevalence of live-born infants with DS having a severe CHD in the Norwegian population over the last 20 years and compare outcomes in infants with AVSD with and without DS. Material and Methods Information on all births from January 1, 2000 to December 31, 2019 was obtained from the Medical Birth Registry of Norway. We also obtained data on all infants with severe CHDs in Norway registered in Oslo University Hospital's Clinical Registry for Congenital Heart Defects during 2000–2019 and accessed individual-level patient data from the electronic hospital records of selected cases. Infants with AVSD and DS were compared to infants with AVSD without chromosomal defects. Crude and adjusted odds ratios (ORs) of infant mortality and need for surgery during the first year of life, with associated 95% confidence intervals (CIs), were estimated by logistic regression. Results A total of 1 177 926 infants were live-born in Norway during the study period. Among these, 1456 (0.1%) had DS. The prevalence of infants with DS having a severe CHDs was relatively stable, with a mean of 17 cases per year. The most common CHD associated with DS was AVSD (44.4%). Infants with AVSD and DS were more likely to have cardiac intervention during their first year of life compared to infants with AVSD without chromosomal defects (adjusted OR [aOR]: 2.52; 95% CI 1.27, 4.98). However, we observed no difference in infant mortality during first year of life between the two groups (aOR: 1.08; 95% CI 0.43, 2.70). Conclusions The prevalence of live-born infants with severe CHDs and DS has been stable in Norway across 20 years. Infants with AVSD and DS did not have higher risk of mortality during their first year of life compared to infants with AVSD without chromosomal defects, despite a higher risk of operative intervention.

• Rasooli, Reza; Holmstrøm, Henrik; Giljarhus, Knut Erik Teigen; Jolma, Ingunn Westvik; Vinningland, Jan Ludvig & Lange, Charlotte De [Show all 8 contributors for this article] (2024). In vitro hemodynamic performance of a blood pump for self-powered venous assist in univentricular hearts. Scientific Reports. 14(1). doi: 10.1038/s41598-024-57269-7. Full text in Research Archive Show summary

  Univentricular heart anomalies represent a group of severe congenital heart defects necessitating early surgical intervention in infancy. The Fontan procedure, the final stage of single-ventricle palliation, establishes a serial connection between systemic and pulmonary circulation by channeling venous return to the lungs. The absence of the subpulmonary ventricle in this peculiar circulation progressively eventuates in failure, primarily due to chronic elevation in inferior vena cava (IVC) pressure. This study experimentally validates the effectiveness of an intracorporeally-powered venous ejector pump (VEP) in reducing IVC pressure in Fontan patients. The VEP exploits a fraction of aortic flow to create a jet-venturi effect for the IVC, negating the external power requirement and driveline infections. An invitro Fontan mock-up circulation loop is developed and the impact of VEP design parameters and physiological conditions is assessed using both idealized and patient-specific total cavopulmonary connection (TCPC) phantoms. The VEP performance in reducing IVC pressure exhibited an inverse relationship with the cardiac output and extra-cardiac conduit (ECC) size and a proportional relationship with the transpulmonary pressure gradient (TPG) and mean arterial pressure (MAP). The ideal VEP with fail-safe features provided an IVC pressure drop of 1.82 ± 0.49, 2.45 ± 0.54, and 3.12 ± 0.43 mm Hg for TPG values of 6, 8, and 10 mm Hg, respectively, averaged over all ECC sizes and cardiac outputs. Furthermore, the arterial oxygen saturation was consistently maintained above 85% during full-assist mode. These results emphasize the potential utility of the VEP to mitigate elevated venous pressure in Fontan patients.

• Holmstrøm, Henrik; Moen, Atle & Tscherning, Charlotte (2024). The term haemodynamic significance should be avoided when treating premature infants with patent ductus arteriosus. Acta Paediatrica. ISSN 0803-5253. 113(11), p. 2340–2341. doi: 10.1111/apa.17401. Full text in Research Archive
• Alecu, Andreea Ioana; Brekke, Idunn; Holmstrøm, Henrik & Syse, Astri (2024). Uptake of cash benefits among children with a disability in Norway: The role of parental socioeconomic characteristics and immigrant background. International Journal of Social Welfare. ISSN 1369-6866. 34(2). doi: 10.1111/ijsw.12705. Full text in Research Archive Show summary

  Caring for a disabled child involves both indirect and direct economic costs, which in turn may create a financial burden for the family. Using Norway as a case, we examine if public compensatory measures reach those most in need, by assessing whether socioeconomic disadvantages and immigrant background impact adversely on the uptake of a nationally available cash benefits eligible for parents caring for a child with a disability. We take advantage of national administrative register data on children with a selection of well-defined diagnoses born between 2009 and 2017 (N = 14,469). Our results show nonnegligible, but relatively minor, social inequalities in the uptake of cash benefits related to socioeconomic and immigrant background. Our findings indicate that this state's financial support seems to reach those most in need. However, it is essential to deepen our understanding of how socioeconomic and immigrant backgrounds influence access to and utilization of municipal healthcare services. Notably, the application process for these services often involves a greater degree of discretion on the part of welfare professionals. Further research is needed to illuminate the nuanced dynamics of these factors in the context of accessing healthcare services at the local level.

• Erikssen, Gunnar; Liestøl, Knut; Aboulhosn, Jamil; Holmstrøm, Henrik; Wik, Gunnar & Døhlen, Gaute [Show all 14 contributors for this article] (2023). Preoperative versus postoperative survival in patients with univentricular heart: A nationwide, retrospective study of patients born in 1990-2015. BMJ Open. 13(7). doi: 10.1136/bmjopen-2022-069531. Full text in Research Archive Show summary

  Objectives Few data exist on mortality among patients with univentricular heart (UVH) before surgery. Our aim was to explore the results of intention to perform surgery by estimating preoperative vs postoperative survival in different UVH subgroups. Design Retrospective. Setting Tertiary centre for congenital cardiology and congenital heart surgery. Participants All 595 Norwegian children with UVH born alive from 1990 to 2015, followed until 31 December 2020. Results One quarter (151/595; 25.4%) were not operated. Among these, only two survived, and 125/149 (83.9%) died within 1 month. Reasons for not operating were that surgery was not feasible in 31.1%, preoperative complications in 25.2%, general health issues in 23.2% and parental decision in 20.5%. In total, 327/595 (55.0%) died; 283/327 (86.5%) already died during the first 2 years of life. Preoperative survival varied widely among the UVH subgroups, ranging from 40/65 (61.5%) among patients with unbalanced atrioventricular septal defect to 39/42 (92.9%) among patients with double inlet left ventricle. Postoperative survival followed a similar pattern. Postoperative survival among patients with hypoplastic left heart syndrome (HLHS) improved significantly (5-year survival, 42.5% vs 75.3% among patients born in 1990–2002 vs 2003–2015; p&lt;0.0001), but not among non-HLHS patients (65.7% vs 72.6%; p=0.22)—among whom several subgroups had a poor prognosis similar to HLHS. A total of 291/595 patients (48.9%) had Fontan surgery Conclusions Surgery was refrained in one quarter of the patients, among whom almost all died shortly after birth. Long-term prognosis was largely determined during the first 2 years. There was a strong concordance between preoperative and postoperative survival. HLHS survival was improved, but non-HLHS survival did not change significantly. This study demonstrates the complications and outcomes encountering newborns with UVH at all major stages of preoperative and operative treatment.

• Solvin, Håvard Bjerkeseth; Diab, Simone; Elle, Ole Jakob; Holmstrøm, Henrik & Brun, Henrik (2023). Real-Time Remote-Mentored Echocardiography in Management of Newborns with Critical Congenital Heart Defects. Congenital Heart Disease. ISSN 1747-079X. 18(5), p. 551–559. doi: 10.32604/chd.2023.031537. Full text in Research Archive Show summary

  Background: The management of suspected critical congenital heart defects (CCHD) relies on timely echocardiographic diagnosis. The availability of experienced echocardiographers is limited or even non-existent in many hospitals with obstetric units. This study evaluates remote-mentored echocardiography performed by physicians without experience in imaging of congenital heart defects (CHD). Methods: The setup included a pediatric cardiologist in a separate room, guiding a physician without experience in echocardiographic imaging of CHD in the examination of a symptomatic newborn. This remote-mentoring pair was blinded to the diagnosis of the newborn and presented with a simplified patient history. The echocardiographic images were streamed to the laptop of the mentor, along with a webcam feed showing the probe position. The task was to identify CCHD in need of immediate transfer to a pediatric cardiac surgical center. The result was compared to the previously completed echocardiographic report and the clinical decision of the patient-responsible pediatric cardiologist. Results: During 17 months, 15 newborns were recruited. All six newborns with CCHD were correctly labeled by the remotementoring pair. One newborn with Tetralogy of Fallot was erroneously labeled as needing immediate transfer. Eight newborns without CCHD were correctly labeled. Conclusions: Remote-mentored echocardiography performed by examiners without experience in imaging CHD identified all newborns with CCHD in need of immediate transfer for specialist care. The setup shows promising results for improving the management of CCHD in hospitals without continuous pediatric cardiology service.

• Rasooli, Reza; Giljarhus, Knut Erik Teigen; Hiorth, Aksel; Jolma, Ingunn Westvik; Vinningland, Jan Ludvig & Lange, Charlotte de [Show all 8 contributors for this article] (2023). In Silico Evaluation of a Self-powered Venous Ejector Pump for Fontan Patients. Cardiovascular Engineering and Technology. ISSN 1869-408X. 14(3), p. 428–446. doi: 10.1007/s13239-023-00663-5. Full text in Research Archive Show summary

  Purpose The Fontan circulation carries a dismal prognosis in the long term due to its peculiar physiology and lack of a subpulmonic ventricle. Although it is multifactorial, elevated IVC pressure is accepted to be the primary cause of Fontan's high mortality and morbidity. This study presents a self-powered venous ejector pump (VEP) that can be used to lower the high IVC venous pressure in single-ventricle patients. Methods A self-powered venous assist device that exploits the high-energy aortic flow to lower IVC pressure is designed. The proposed design is clinically feasible, simple in structure, and is powered intracorporeally. The device's performance in reducing IVC pressure is assessed by conducting comprehensive computational fluid dynamics simulations in idealized total cavopulmonary connections with different offsets. The device was finally applied to complex 3D reconstructed patient-specific TCPC models to validate its performance. Results The assist device provided a significant IVC pressure drop of more than 3.2 mm Hg in both idealized and patient-specific geometries, while maintaining a high systemic oxygen saturation of more than 90%. The simulations revealed no significant caval pressure rise (< 0.1 mm Hg) and sufficient systemic oxygen saturation (> 84%) in the event of device failure, demonstrating its fail-safe feature. Conclusions A self-powered venous assist with promising in silico performance in improving Fontan hemodynamics is proposed. Due to its passive nature, the device has the potential to provide palliation for the growing population of patients with failing Fontan.

• Wik, Gunnar; Jortveit, Jarle; Sitras, Vasilis; Perminow, Karl Viktor; Pripp, Are Hugo & Døhlen, Gaute [Show all 8 contributors for this article] (2023). Detection of severe congenital heart defects in live-born infants in Norway 2017–2020. Acta Paediatrica. ISSN 0803-5253. 113(1), p. 135–142. doi: 10.1111/apa.16953. Full text in Research Archive
• Solvin, Håvard; Lippert, Matthias; Holmstrøm, Henrik; Elle, Ole Jakob & Brun, Henrik (2023). Real-time Remote Expert-guided Echocardiography by Medical Students. Ultrasound Journal. 15(1). doi: 10.1186/s13089-023-00328-3. Full text in Research Archive Show summary

  Background Echocardiography is a highly specialised examination performed by experienced healthcare professionals. These experienced healthcare professionals may not be available to patients during all hours in rural healthcare facilities. Remote-guided echocardiography could improve the availability of specialised care for patients living in rural areas. This study examined the feasibility of real-time remote guidance for medical students to perform an echocardiographic assessment of the left side of the heart. Thirteen healthy volunteers were recruited for remote-guided echocardiography, which was performed by 13 medical students. Student examinations/images were compared to reference echocardiography. Measurements of left ventricular fractional shortening and mitral valve blood flow velocity were also compared. Furthermore, guidance through a smartphone videoconference was compared to designated remote guidance software. Results Two-thirds of the images acquired by students were rated as medium or good quality and usable to evaluate two thirds of the cardiac structures. No significant bias was found for left ventricular fractional shortening. The measurements from the students’ exams had a variation coefficient of 14.8% compared to the reference. The calculated deviation of the insonation angle was above 25° for both E and A-wave mitral valve blood flow velocity measurements. Images acquired by guidance through smartphone videoconference were of lower quality than those obtained using the designated remote guidance software. Conclusion Real-time remote-guided echocardiography performed by medical students has limited value for clinical screening but could be useful for educational purposes. Graphical Abstract

• Hjorth-Johansen, Elin; Børøsund, Elin; Martinsen, Ingeborg; Holmstrøm, Henrik & Moen, Anne (2023). Acceptability and Initial Adoption of the Heart Observation App for Infants With Congenital Heart Disease: Qualitative Study. JMIR Formative Research. 7, p. 1–15. doi: 10.2196/45920. Full text in Research Archive Show summary

  Background: Approximately 1% of all infants are born with a congenital heart disease (CHD). Internationally CHD remains a major cause of infant death, some of which occur unexpectedly after a gradual deterioration at home. Many parents find it difficult to recognize worsening of symptoms. Objective: This study aims to report the acceptability and initial adoption of a mobile app, the Heart Observation app (HOBS), aiming to support parents’ understanding and management of their child’s condition and to increase quality in follow-up from health care professionals in complex health care services in Norway. Methods: A total of 9 families were interviewed on discharge from the neonatal intensive care unit and after 1 month at home. The infant’s primary nurse, community nurse, and cardiologist were also interviewed regarding their experiences about collaboration with the family. The interviews were analyzed inductively with thematic content analysis. Results: The analysis generated 4 main themes related to acceptability and adoption: (1) Individualize Initial Support, (2) Developing Confidence and Coping, (3) Normalize When Appropriate, and (4) Implementation in a Complex Service Pathway. The receptivity of parents to learn and attend in the intervention differs according to their present situation. Health care professionals emphasized the importance of adapting the introduction and guidance to parents’ receptivity to ensure comprehension, self-efficacy, and thereby acceptance before discharge (Individualize Initial Support). Parents perceived that HOBS served them well and nurtured confidence by teaching them what to be aware of. Health care professionals reported most parents as confident and informed. This potential effect increased the possibility of adoption (Developing Confidence and Coping). Parents expressed that HOBS was not an “everyday app” and wanted to normalize everyday life when appropriate. Health care professionals suggested differentiating use according to severity and reducing assessments after recovery to adapt the burden of assessments when appropriate (Normalize When Appropriate). Health care professionals’ attitude to implement HOBS in their services was positive. They perceived HOBS as useful to systemize guidance, to enhance communication regarding an infant’s condition, and to increase understanding of heart defects in health care professionals with sparse experience (Implementation in a Complex Service Pathway). Conclusions: This feasibility study shows that both parents and health care professionals found HOBS as a positive addition to the health care system and follow-up. HOBS was accepted and potentially useful, but health care professionals should guide parents initially to ensure comprehension and adapt timing to parents’ receptivity. By doing so, parents may be confident to know what to look for regarding their child’s health and cope at home. Differentiating between various diagnoses and severity is important to support normalization when appropriate. Further controlled studies are needed to assess adoption, usefulness, and benefits in the health care system

• Holten-Andersen, Mads Nikolaj; Lippert, Matthias; Holmstrøm, Henrik; Brun, Henrik & Døhlen, Gaute (2022). Current outcomes of live-born children with double outlet right ventricle in Norway. European Journal of Cardio-Thoracic Surgery. ISSN 1010-7940. 63(1). doi: 10.1093/ejcts/ezac560. Full text in Research Archive Show summary

  Objectives: This population-based, comprehensive, retrospective study presented the clinical outcomes of all children born in Norway between 2003 and 2017 with double outlet right ventricle (DORV). Methods: All children born with DORV between 2003 and 2017 were identified in the Oslo University Hospital registry. Patients' characteristics, interventions, complications and deaths were recorded. Echocardiographic data were reviewed for classification according to current standards. We investigated time-dependent surgical reintervention and mortality using Kaplan-Meier analyses and determinants of treatment complications, reintervention and death using regression analyses. Results: Ninety-three children with DORV represented an annual median prevalence of 1.18 per 10 000 births in Norway. Six children received palliative care. With an intention to treat, a surgical route with the primary biventricular repair was followed for 62 children, staged biventricular repair for 15 and univentricular repair for 10 children. Major complications occurred in 1.0% and 6.2% of children following catheter or surgical intervention, respectively. No significant determinants of the complications were identified. Overall survival following treatment was 91.9%, 90.8%, 89.5% and 89.5% and corresponding freedom from surgical reintervention was 88.0%, 79.0%, 74.9% and 69.4% at 1, 2, 5 and 10 years, respectively. The presence of atrioventricular septal defect predicted an increased risk of mortality (hazard ratio: 7.16) but did not increase the risk of surgical reintervention. Conclusions: In Norway, most children receive tailored treatment for DORV with low rates of complications, surgical reinterventions and mortality. However, atrioventricular septal defect remains a potential determinant of postoperative death. Keywords: Biventricular; Complication; DORV; Double outlet right ventricle; Reintervention; Univentricular. © The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.

• Hjorth-Johansen, Elin; Børøsund, Elin; Moen, Anne; Anna, Harmens; Martinsen, Ingeborg & Wik, Gunnar [Show all 9 contributors for this article] (2022). Heart OBServation app: development of a decision support tool for parents of infants with severe cardiac disease. Cardiology in the Young. ISSN 1047-9511. 33(8), p. 1350–1358. doi: 10.1017/S1047951122002438. Full text in Research Archive Show summary

  Background and objectives: Many parents of infants with CHD find it difficult to recognise symptoms of deterioration in their children. Therefore, a personalised decision support application for parents has been developed. This application aims to increase parents’ awareness of their infant’s normal condition, help them assess signs of deterioration, decide who and when to contact health services, and what to report. The aim of this paper is to describe the concept and report results from a usability study. Methods: An interprofessional group developed a mobile application called the Heart OBServation app in close collaboration with parents using an iterative process. We performed a usability study consisting of semi-structured interviews of 10 families at discharge and after one month and arranged two focus group interviews with nurses caring for these families. Athematic framework analysis of the interviews explored the usability of features in the application. Usability was assessed twice using the System Usability Scale, and a user log was registered throughout the study. Results: The overall system usability score, 82.3 after discharge and 81.7 after one month, indicates good system usability. The features of Heart OBServation were perceived as useful to provide tailored information, increase awareness of the child’s normal condition, and to guide parents in what to look for. To empower parents, an interactive discharge checklist was added. Conclusions: The Heart OBServation demonstrated good usability and was well received by parents and nurses. Feasibility and benefits of this application in clinical practice will be investigated in further studies

• Möller, Thomas; Klungerbo, Vibeke; Diab, Simone; Holmstrøm, Henrik; Edvardsen, Elisabeth & Grindheim, Guro [Show all 11 contributors for this article] (2021). Circulatory Response to Rapid Volume Expansion and Cardiorespiratory Fitness in Fontan Circulation. Pediatric Cardiology. ISSN 0172-0643. doi: 10.1007/s00246-021-02802-y. Full text in Research Archive Show summary

  The role of dysfunction of the single ventricle in Fontan failure is incompletely understood. We aimed to evaluate hemodynamic responses to preload increase in Fontan circulation, to determine whether circulatory limitations in different locations identified by experimental preload increase are associated with cardiorespiratory fitness (CRF), and to assess the impact of left versus right ventricular morphology. In 38 consecutive patients (median age = 16.6 years, 16 females), heart catheterization was supplemented with a rapid 5-mL/kg body weight volume expansion. Central venous pressure (CVP), ventricular end-diastolic pressure (VEDP), and peak systolic pressure were averaged for 15‒30 s, 45‒120 s, and 4‒6 min (steady state), respectively. CRF was assessed by peak oxygen consumption (VO2peak) and ventilatory threshold (VT). Median CVP increased from 13 mmHg at baseline to 14.5 mmHg (p < 0.001) at steady state. CVP increased by more than 20% in eight patients. Median VEDP increased from 10 mmHg at baseline to 11.5 mmHg (p < 0.001). Ten patients had elevated VEDP at steady state, and in 21, VEDP increased more than 20%. The transpulmonary pressure difference (CVP‒VEDP) and CVP were consistently higher in patients with right ventricular morphology across repeated measurements. CVP at any stage was associated with VO2peak and VT. VEDP after volume expansion was associated with VT. Preload challenge demonstrates the limitations beyond baseline measurements. Elevation of both CVP and VEDP are associated with impaired CRF. Transpulmonary flow limitation was more pronounced in right ventricular morphology. Ventricular dysfunction may contribute to functional impairment after Fontan operation in young adulthood.

• Wendel, Kristina; Pfeiffer, Helle Cecilie; Fugelseth, Drude; Nestaas, Eirik; Domellöf, Magnus & Skålhegg, Bjørn Steen [Show all 42 contributors for this article] (2021). Effects of nutrition therapy on growth, inflammation and metabolism in immature infants: a study protocol of a double-blind randomized controlled trial (ImNuT). BMC Pediatrics. 21. doi: 10.1186/s12887-020-02425-x. Full text in Research Archive Show summary

  Background: Current nutritional management of infants born very preterm results in significant deficiency of the essential fatty acids (FAs) arachidonic acid (ARA) and docosahexaenoic acid (DHA). The impact of this deficit on brain maturation and inflammation mediated neonatal morbidities are unknown. The aim of this study is to determine whether early supply of ARA and DHA improves brain maturation and neonatal outcomes in infants born before 29 weeks of gestation. Methods: Infants born at Oslo University Hospital are eligible to participate in this double-blind randomized controlled trial. Study participants are randomized to receive an enteral FA supplement of either 0.4 ml/kg MCT-oil™ (medium chain triglycerides) or 0.4 ml/kg Formulaid™ (100 mg/kg of ARA and 50 mg/kg of DHA). The FA supplement is given from the second day of life to 36 weeks' postmenstrual age (PMA). The primary outcome is brain maturation assessed by Magnetic Resonance Imaging (MRI) at term equivalent age. Secondary outcomes include quality of growth, incidence of neonatal morbidities, cardiovascular health and neuro-development. Target sample size is 120 infants (60 per group), this will provide 80% power to detect a 0.04 difference in mean diffusivity (MD, mm2/sec) in major white matter tracts on MRI. Discussion: Supplementation of ARA and DHA has the potential to improve brain maturation and reduce inflammation related diseases. This study is expected to provide valuable information for future nutritional guidelines for preterm infants. Trial registration: Clinicaltrials.gov ID: NCT03555019 . Registered 4 October 2018- Retrospectively registered.

• Thrane, Karl Julius; Müller, Lil-Sofie Ording; Suther, Lene Kathrine R; Thomassen, Kristian Stien; Holmstrøm, Henrik & Thaulow, Erik [Show all 9 contributors for this article] (2021). Spectrum of Fontan‑associated liver disease assessed by MRI and US in young adolescents. Abdominal Radiology. ISSN 2366-004X. 46, p. 3205–3216. doi: 10.1007/s00261-021-02994-0. Full text in Research Archive Show summary

  Abstract Purpose Patients with Fontan circulation are at risk of developing hepatic fibrosis/cirrhosis. The mechanisms and disease development are unclear and early secondary liver cancer is a concern. This study will describe hepatic imaging findings in a national cohort of adolescents with Fontan circulation. Methods The patients prospectively underwent abdominal contrast enhanced magnetic resonance imaging (MRI) including diffusion-weighted imaging. Images were assessed for criteria of fibrosis / cirrhosis including characterization of hepatic nodules. These nodules were in addition, assessed by ultrasonography (US). Nodules ≥ 1 cm were investigated and monitored to evaluate malignant transformation. Clinical and hepatic serological data were recorded. Results Forty-six patients, median age of 16.5 years (15.4–17.9 years) were enrolled. All patients underwent US examination and MRI was performed in 35/46 patients. On MRI, 60% had hepatomegaly and 37% had signs of fibrosis/cirrhosis. Seven patients had together 13 nodules ≥ 1 cm in diameter. Only 4/13 (17%) where seen on US. Nodules had variable MRI signal characteristics including hepatobiliary contrast enhancement and two nodules revealed portal venous phase ‘wash-out’ on the first examination. No further imaging signs of malignancy were revealed during the follow-up period of median 24.4 (7–42) months. Conclusion The majority of adolescents with Fontan circulation had imaging findings of fibrosis/cirrhosis of varying severity. US had low detection rate of hepatic nodules compared to MRI. The imaging work-up before transition to adult cardiology care did not reveal findings suggestive of malignancy. However, the high prevalence of Fontan-associated liver disease calls for surveillance strategies even in childhood.

• Wik, Gunnar; Jortveit, Jarle; Sitras, Vasilis; Døhlen, Gaute; Rønnestad, Arild Erlend & Holmstrøm, Henrik (2021). Unexpected death in children with severe congenital heart defects in Norway 2004-2016. Archives of Disease in Childhood. ISSN 0003-9888. 106, p. 961–966. doi: 10.1136/archdischild-2020-319936. Full text in Research Archive
• Wik, Gunnar; Jortveit, Jarle; Sitras, Vasilis; Døhlen, Gaute; Rønnestad, Arild Erlend & Holmstrøm, Henrik (2020). Severe congenital heart defects: Incidence, causes and time trends of preoperative mortality in Norway. Archives of Disease in Childhood. ISSN 0003-9888. 105(8), p. 738–743. doi: 10.1136/archdischild-2019-317581. Full text in Research Archive
• Jortveit, Jarle; Eskedal, Leif Torvald; Klcovansky, Jakob; Døhlen, Gaute & Holmstrøm, Henrik (2019). Forekomst av infeksiøs endokarditt hos barn. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 139(2), p. 1–5. doi: 10.4045/tidsskr.18.0422. Full text in Research Archive
• Dale, Maria Teresa Grønning; Magnus, Per; Leirgul, Elisabeth; Holmstrøm, Henrik; Gjessing, Håkon K. & Brodwall, Kristoffer [Show all 9 contributors for this article] (2019). Intake of sucrose‑sweetened soft beverages during pregnancy and risk of congenital heart defects (CHD) in offspring: A Norwegian pregnancy cohort study. European Journal of Epidemiology (EJE). ISSN 0393-2990. 34(4), p. 383–396. doi: 10.1007/s10654-019-00480-y. Full text in Research Archive Show summary

  Studies report increased risk of congenital heart defects (CHD) in the offspring of mothers with diabetes, where high blood glucose levels might confer the risk. We explored the association between intake of sucrose-sweetened soft beverages during pregnancy and risk of CHD. Prospective cohort data with 88,514 pregnant women participating in the Norwegian Mother and Child Cohort Study was linked with information on infant CHD diagnoses from national health registers and the Cardiovascular Diseases in Norway Project. Risk ratios were estimated by fitting generalized linear models and generalized additive models. The prevalence of children with CHD was 12/1000 in this cohort (1049/88,514). Among these, 201 had severe and 848 had non-severe CHD (patent ductus arteriosus; valvular pulmonary stenosis; ventricular septal defect; atrial septal defect). Only non-severe CHD was associated with sucrose-sweetened soft beverages. The adjusted risk ratios (aRR) for non-severe CHD was 1.30 (95% CI 1.07–1.58) for women who consumed 25–70 ml/day and 1.27 (95% CI 1.06–1.52) for women who consumed ≥ 70 ml/day when compared to those drinking ≤ 25 ml/day. Dose–response analyses revealed an association between the risk of non-severe CHD and the increasing exposure to sucrose-sweetened soft beverages, especially for septal defects with aRR = 1.26 (95% CI 1.07–1.47) per tenfold increase in daily intake dose. The findings persisted after adjustment for maternal diabetes or after excluding mothers with diabetes (n = 19). Fruit juices, cordial beverages and artificial sweeteners showed no associations with CHD. The findings suggest that sucrose-sweetened soft beverages may affect the CHD risk in offspring.

• Jortveit, Jarle; Wik, Gunnar; Ødegaard, Jostein Strand; Sitras, Vasilis; Perminow, Karl Viktor & Holmstrøm, Henrik (2019). Diagnostikk av alvorlige medfødte hjertefeil i Norge 2016. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 139(2). doi: 10.4045/tidsskr.18.0606. Full text in Research Archive
• Indrebø, Marianne Muller; Berg, Ansgar; Holmstrøm, Henrik; Seem, Egil; Guthe, Hans Jørgen & Wiig, Helge [Show all 7 contributors for this article] (2019). Fluid accumulation in the staged Fontan procedure: the impact of colloid osmotic pressures. Interactive Cardiovascular and Thoracic Surgery. ISSN 1569-9293. 28(4), p. 510–517. doi: 10.1093/icvts/ivy298. Full text in Research Archive
• Jortveit, Jarle; Klcovansky, Jakob; Eskedal, Leif Torvald; Birkeland, Sigurd; Døhlen, Gaute & Holmstrøm, Henrik (2018). Endocarditis in children and adolescents with congenital heart defects - a Norwegian nationwide register-based cohort study. Archives of Disease in Childhood. ISSN 0003-9888. 103(7), p. 670–674. doi: 10.1136/archdischild-2017-313917. Full text in Research Archive Show summary

  Objectives: Congenital heart defects (CHD) are the most common birth defects worldwide and are an important cause of morbidity and early death. A significant number of deaths occur among patients with infections. CHDs predispose to the development of infective endocarditis (IE) and represent a risk factor for increased mortality due to IE. The aim of this study was to investigate the occurrence and outcomes of IE in children and adolescents with CHDs. Methods: Data on all children with CHD and IE born in Norway between 1994 and 2016 were retrieved from the Oslo University Hospital’s Clinical Registry for Congenital Heart Defects. Survivors were followed through 2016, and supplementary information was retrieved from medical records. Results: In this nationwide register-based cohort study, which included all 1 357 543 live births in Norway between 1994 and 2016, the incidence of IE according to the European Society of Cardiology diagnostic criteria was 2.2 per 10 000 person-years among children and adolescents with CHDs. The incidence was stable throughout the period. Most patients with IE had severe CHDs (75%) and had undergone open chest cardiac surgery or catheter-based cardiac interventions the last year before IE. IE-related mortality among children with CHDs and IE was 8% during the follow-up period (mean 12.4 years (±5.5 years)). Conclusions: The incidence of IE among children and adolescents with CHDs was higher than the reported incidence in the general population. IE was associated with severe CHDs and recent complex cardiac interventions, and had significant mortality.

• Jortveit, Jarle; Klcovansky, Jakob; Døhlen, Gaute; Eskedal, Leif Torvald; Birkeland, Sigurd & Holmstrøm, Henrik (2018). Out-of-hospital sudden cardiac arrest in children with congenital heart defects. Archives of Disease in Childhood. ISSN 0003-9888. 103(1), p. 57–60. doi: 10.1136/archdischild-2017-312621. Full text in Research Archive
• Möller, Thomas; Lindberg, Harald L; Samersaw-Lund, May Brit; Holmstrøm, Henrik; Døhlen, Gaute & Thaulow, Erik (2018). Right ventricular pressure response to exercise in adults with isolated ventricular septal defect closed in early childhood. Cardiology in the Young. ISSN 1047-9511. 28(6), p. 797–803. doi: 10.1017/S1047951117002979. Full text in Research Archive Show summary

  We previously demonstrated an abnormally high right ventricular systolic pressure response to exercise in 50% of adolescents operated on for isolated ventricular septal defect. The present study investigated the prevalence of abnormal right ventricular systolic pressure response in 20 adult (age 30–45 years) patients who underwent surgery for early ventricular septal defect closure and its association with impaired ventricular function, pulmonary function, or exercise capacity. The patients underwent cardiopulmonary tests, including exercise stress echocardiography. Five of 19 patients (26%) presented an abnormal right ventricular systolic pressure response to exercise ⩾ 52 mmHg. Right ventricular systolic function was mixed, with normal tricuspid annular plane systolic excursion and fractional area change, but abnormal tricuspid annular systolic motion velocity (median 6.7 cm/second) and isovolumetric acceleration (median 0.8 m/second2). Left ventricular systolic and diastolic function was normal at rest as measured by the peak systolic velocity of the lateral wall and isovolumic acceleration, early diastolic velocity, and ratio of early diastolic flow to tissue velocity, except for ejection fraction (median 53%). The myocardial performance index was abnormal for both the left and right ventricle. Peak oxygen uptake was normal (mean z score −0.4, 95% CI −2.8–0.3). There was no association between an abnormal right ventricular systolic pressure response during exercise and right or left ventricular function, pulmonary function, or exercise capacity. Abnormal right ventricular pressure response is not more frequent in adult patients compared with adolescents. This does not support the theory of progressive pulmonary vascular disease following closure of left-to-right shunts.

• Granlund, Peder Annæus; Ødegaard, Jostein Strand; Skjerven, Håvard Ove; Carlsen, Karin C. Lødrup; Hanséus, Katarina & Rögnvaldsson, Ingolfur [Show all 9 contributors for this article] (2018). Survey of 23 Nordic university hospitals showed that 77% lacked written procedures for measuring and interpreting blood pressure in infants. Acta Paediatrica. ISSN 0803-5253. 108(2), p. 266–270. doi: 10.1111/apa.14492. Full text in Research Archive Show summary

  Aim: This study determined the use of standardised procedures for infant noninvasive blood pressure (NIBP) measurements in the Nordic countries and aimed to identify factors included in the standardisation and interpretation of NIBP measurements in infants. Methods: A cross‐sectional electronic questionnaire survey was sent to 84 physicians in all 23 university hospitals in Sweden, Norway, Denmark, Finland and Iceland and was completed from February to March 2017. The survey contained respondent characteristics, the presence and description of standardised procedures for NIBP measurements, daily practice of NIBP measurements and methodological considerations and interpretation of NIBP measurements in a healthy six‐month‐old child. Results: We received responses from 55 of 84 physicians working in all 23 Nordic university hospitals, in paediatric cardiology (n = 22), general paediatrics (n = 16), paediatric nephrology (n = 14) and other fields (n = 3). Less than a quarter (23%) said their hospital issued specific NIBP procedures relating to infants and they referred to 19 different sources of information. The factors that were most commonly assessed for interpretation were age (100%), arousal state (78%) and cuff size (76%). Conclusion: Most of the university hospital units treating children lacked age‐specific written procedures for measuring and interpreting infant NIBP, and there is a strong need for common Nordic guidelines.

• Brodwall, Kristoffer; Greve, Gottfried; Leirgul, Elisabeth; Klungsøyr, Kari; Holmstrøm, Henrik & Vollset, Stein Emil [Show all 7 contributors for this article] (2018). The five-year survival of children with Down syndrome in Norway 1994-2009 differed by associated congenital heart defects and extracardiac malformations. Acta Paediatrica. ISSN 0803-5253. 107(5), p. 845–853. doi: 10.1111/apa.14223. Full text in Research Archive
• Øyen, Anne-Siri; Ulleberg, Bente; Sangar, Paul; Wallace, Sean Ciaran & Holmstrøm, Henrik (2017). En gutt med hjertefeil og atferdsvansker. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. doi: 10.4045/tidsskr.17.0198. Full text in Research Archive
• Indrebø, Marianne Muller; Berg, Ansgar; Holmstrøm, Henrik; Seem, Egil; Guthe, Hans Jørgen & Wiig, Helge [Show all 7 contributors for this article] (2017). Fluid accumulation after closure of atrial septal defects: the role of colloid osmotic pressure. Interactive Cardiovascular and Thoracic Surgery. ISSN 1569-9293. 26(2), p. 307–312. doi: 10.1093/icvts/ivx334. Full text in Research Archive
• Hjortshøj, Cristel Marie Sørensen; Jensen, Anette Schophuus; Sørensen, Keld; Nagy, Edit; Johansson, Bengt & Kronvall, Thomas [Show all 12 contributors for this article] (2017). Epidemiological changes in Eisenmenger syndrome in the Nordic region 1977-2012. Heart. ISSN 1355-6037. 103(17), p. 1353–1358. doi: 10.1136/heartjnl-2016-310979. Full text in Research Archive
• Ravndal, Maren Emilie Aaland; Christensen, Anders Haugom; Døhlen, Gaute & Holmstrøm, Henrik (2017). Paediatric cardiac catheterisation in Norway: Rates and types of complications in new terms. Cardiology in the Young. ISSN 1047-9511. 27(7), p. 1329–1335. doi: 10.1017/S1047951117000208. Full text in Research Archive Show summary

  We determined the incidence, type, and severity of complications after cardiac catheterisation in children with heart disease in Norway, and we present the results in terms of the International Paediatric and Congenital Cardiac Code (IPCCC) nomenclature for complications. All paediatric cardiac catheterisations in Norway are performed in one clinical centre. All procedures performed during a 5-year period beginning in 2010 were prospectively registered, and medical records for cases with complications were reviewed to confirm the event and to re-classify the type, severity, and attributability of the complication according to the IPCCC nomenclature. Univariate and multivariate analyses were performed to identify possible risk predictors. A total of 1318 catheterisations performed on 941 patients were included in the present study, of which 68% were interventional. The complication and major complication rates were 5.5 and 1.4%, respectively. Trauma to the vessels or the myocardium, haemodynamic adverse events, and arrhythmias were the most common types of complications. In the multivariate model, weight <4 kg (odds ratios, 3.0; 95% confidence intervals: 1.6–5.8) and risk category 5 (odds ratios, 5.1; 95% confidence intervals: 2.1–12.3) were significant risk predictors for any complication. In spite of a high rate of interventions, the complication rates in this study were similar to older studies, but diverging methods and terminology limit the comparability. We strongly suggest general use of the proposed IPCCC classification system for registration and reports of complications for paediatric cardiac catheterisations.

• Hjortshøj, Cristel Marie Sørensen; Kempny, Aleksander; Jensen, Anette Schophuus; Sørensen, Keld; Nagy, Edit & Dellborg, Mikael [Show all 23 contributors for this article] (2017). Past and current cause-specific mortality in Eisenmenger syndrome. European Heart Journal. ISSN 0195-668X. 38(26), p. 2060–2067. doi: 10.1093/eurheartj/ehx201. Full text in Research Archive
• Brekke, Idunn; Früh, Elena Albertini; Kvarme, Lisbeth Gravdal & Holmstrøm, Henrik (2017). Long-time sickness absence among parents of pre-school children with cerebral palsy, spina bifida and down syndrome: a longitudinal study. BMC Pediatrics. 17(26). doi: 10.1186/s12887-016-0774-8. Full text in Research Archive
• Jortveit, Jarle; Leirgul, Elisabeth; Eskedal, Leif Torvald; Greve, Gottfried; Fomina, Tatiana & Døhlen, Gaute [Show all 10 contributors for this article] (2016). Mortality and complications in 3495 children with isolated ventricular septal defects. Archives of Disease in Childhood. ISSN 0003-9888. 101(9), p. 808–813. doi: 10.1136/archdischild-2015-310154. Full text in Research Archive
• Leirgul, Elisabeth; Brodwall, Kristoffer; Greve, Gottfried; Vollset, Stein Emil; Holmstrøm, Henrik & Tell, Grethe S. [Show all 7 contributors for this article] (2016). Maternal Diabetes, Birth Weight, and Neonatal Risk of Congenital Heart Defects in Norway, 1994-2009. Obstetrics and Gynecology. ISSN 0029-7844. 128(5), p. 1116–1125. doi: 10.1097/AOG.0000000000001694. Full text in Research Archive Show summary

  Objective: To investigate the association between pregestational or gestational diabetes and offspring risk of congenital heart defects and the association between large-for-gestational-age birth weight and risk of cardiac defects in offspring of diabetic women. Methods: Information on pregestational and gestational diabetes, cardiac defects, and birth weight among all births in Norway in 1994–2009 was ascertained from the Medical Birth Registry of Norway, national health registries, and the Cardiovascular Disease in Norway project. The relative risk (RR) compared offspring risk of cardiac defects for maternal diabetes with offspring risk in nondiabetic mothers adjusted for year of birth, maternal age, and parity. Results: Among 914,427 births (live births, stillbirths, terminated pregnancies), 5,618 (0.61%) were complicated by maternal pregestational diabetes and 9,726 (1.06%) by gestational diabetes. Congenital heart defects were identified in 10,575 offspring. The prevalence of cardiac defects differed between groups: 344 of 10,000 births to women with pregestational diabetes, 172 of 10,000 to women with gestational diabetes, and 114 of 10,000 in women without diabetes (adjusted RRs 2.92, 95% confidence interval [CI] 2.54–3.36 and 1.47, 95% CI 1.26–1.71). During the study period, the adjusted RRs for congenital heart defects did not change. The risk of cardiac defects in neonates very large for gestational age (birth weight greater than 3 standard deviations above the mean) was compared with neonates with birth weight appropriate for gestational age. For pregestational diabetes, the prevalences of offspring cardiac defects were 561 compared with 248 per 10,000 births (adjusted RR 2.23, 95% CI 1.39–3.59) and for gestational diabetes 388 compared with 132 per 10,000 (adjusted RR 2.73, 95% CI 1.53–4.85). Conclusion: The increased risk of having a child with a congenital heart defect has not changed for diabetic women in Norway since 1994. Among women with pregestational or gestational diabetes, having a large-for-gestational-age neonate was associated with a two- to threefold increased risk of cardiac defects compared with neonates with normal birth weight.

• Fruh, Andreas; Siem, Geir; Holmstrøm, Henrik; Døhlen, Gaute & Haugaa, Kristina (2016). The Jervell and Lange-Nielsen syndrome; atrial pacing combined with ß-blocker therapy, a favorable approach in young high-risk patients with long QT syndrome? Heart Rhythm. ISSN 1547-5271. 13(11), p. 2186–2192. doi: 10.1016/j.hrthm.2016.07.020. Full text in Research Archive
• Wallace, Sean Ciaran; Døhlen, Gaute; Holmstrøm, Henrik; Lund, Christian & Russell, David (2016). Cerebral Microemboli Detection and Differentiation During Transcatheter Closure of Patent Ductus Arteriosus. Pediatric Cardiology. ISSN 0172-0643. 37(6), p. 1141–1147. doi: 10.1007/s00246-016-1410-y. Full text in Research Archive
• Jortveit, Jarle; Eskedal, Leif Torvald; Hirth, Asle; Fomina, Tatiana; Døhlen, Gaute & Hagemo, Petter [Show all 10 contributors for this article] (2016). Sudden unexpected death in children with congenital heart defects. European Heart Journal. ISSN 0195-668X. 37(7), p. 621–626. doi: 10.1093/eurheartj/ehv478. Full text in Research Archive
• Jortveit, Jarle; Øyen, Nina; Leirgul, Elisabeth; Fomina, Tatiana; Tell, Grethe Seppola & Vollset, Stein Emil [Show all 10 contributors for this article] (2016). Trends in Mortality of Congenital Heart Defects. Congenital Heart Disease. ISSN 1747-079X. 11(2), p. 160–168. doi: 10.1111/chd.12307. Full text in Research Archive
• Monclair, Tom; Ruud, Ellen; Holmstrøm, Henrik; Aagenæs, Ingegerd; Asplin, Marius & Beiske, Klaus (2015). Extra-adrenal composite phaeochromocytoma/neuroblastoma in a 15-month-old child. Journal of Pediatric Surgery Case Reports. 3(8), p. 348–350. doi: 10.1016/j.epsc.2015.06.014. Full text in Research Archive
• Leirgul, Elisabeth; Gildestad, Trude; Nilsen, Roy Miodini; Fomina, Tatiana; Brodwall, Kristoffer & Greve, Gottfried [Show all 10 contributors for this article] (2015). Periconceptional folic acid supplementation and infant risk of congenital heart defects in Norway 1999-2009. Paediatric and Perinatal Epidemiology. ISSN 0269-5022. 29(5), p. 391–400. doi: 10.1111/ppe.12212. Full text in Research Archive Show summary

  Background The birth prevalence of congenital heart defects (CHDs) has decreased in Canada and Europe. Recommended intake of folic acid in pregnancy is a suggestive risk-reducing factor for CHDs. We investigated the association between periconceptional intake of folic acid supplements and infant risk of CHDs. Methods Information on maternal intake of folic acid supplements before and during pregnancy in the Medical Birth Registry of Norway 1999–2009 was updated with information on CHD diagnoses from national health registers and the Cardiovascular Diseases in Norway Project. The association between folic acid intake and infant risk of CHD was estimated as relative risk (RR) with binomial log linear regression. Results Among 517 784 non-chromosomal singleton births, 6200 children were identified with CHD and 1153 with severe CHD. For all births, 18.4% of the mothers initiated folic acid supplements before pregnancy and 31.6% during pregnancy. The adjusted RR for severe CHD was 0.99 [95% confidence interval [CI] 0.86, 1.13] comparing periconceptional intake of folic acid with no intake. Specifically, RR for conotruncal defects was 0.99 [95% CI 0.80, 1.22], atrioventricular septal defects 1.19 [95% CI 0.78, 1.81], left ventricular outflow tract obstructions 1.02 [95% CI 0.78, 1.32], and right ventricular outflow tract obstructions 0.97 [95% CI 0.72, 1.29]. Birth prevalence of septal defects was higher in the group exposed to folic acid supplements with RR 1.19 [95% CI 1.10, 1.30]. Conclusions Periconceptional folic acid supplement use showed no association with severe CHDs in the newborn. An unexpected association with an increased risk of septal defects warrants further investigation.

• Brodwall, Kristoffer; Leirgul, Elisabeth; Greve, Gottfried; Vollset, Stein Emil; Holmstrøm, Henrik & Tell, Grethe Seppola [Show all 7 contributors for this article] (2015). Possible Common Aetiology behind Maternal Preeclampsia and Congenital Heart Defects in the Child: a Cardiovascular Diseases in Norway Project Study. Paediatric and Perinatal Epidemiology. ISSN 0269-5022. 30(1), p. 76–85. doi: 10.1111/ppe.12252. Full text in Research Archive Show summary

  http://www.ncbi.nlm.nih.gov/pubmed/26479038

• Leirgul, Elisabeth; Fomina, Tatiana; Brodwall, Kristoffer; Greve, Gottfried; Holmstrøm, Henrik & Vollset, Stein Emil [Show all 8 contributors for this article] (2014). Birth prevalence of congenital heart defects in Norway 1994-2009 - A nationwide study. American Heart Journal. ISSN 0002-8703. 168(6), p. 956–964. doi: 10.1016/j.ahj.2014.07.030. Full text in Research Archive Show summary

  Background: The reasons for decreasing birth prevalence of congenital heart defects (CHDs) in several European countries and Canada are not fully understood. We present CHD prevalence among live births, stillbirths, and terminated pregnancies in an entire nation over a period of 16 years. Methods: Information on all births in the Medical Birth Registry of Norway, 1994-2009, was updated with information on CHD from the hospitals' Patient Administrative Systems, the National Hospital's clinical database for children with heart disease, and the Cause of Death Registry. Individuals with heart defects were assigned specific cardiac phenotypes. Results: Among 954,413 births, 13,081 received a diagnosis of CHD (137.1 per 10,000 births, 133.2 per 10,000 live births). The prevalence per 10,000 births was as follows: heterotaxia, 1.6; conotruncal defects, 11.6; atrioventricular septal defects, 5.6; anomalous pulmonary venous return, 1.1; left outflow obstructions, 8.7; right outflow obstructions, 5.6; septal defects, 65.5; isolated patent ductus arteriosus, 24.6; and other specified or unspecified CHD, 12.7. Excluding preterm patent ductus arteriosus, the CHD prevalence was 123.4 per 10,000; per year, the prevalence increased with 3.5% (95% CI 2.5-4.4) in 1994-2005 and declined with 9.8%(−16.7 to −2.4) from2005 onwards. SevereCHDprevalencewas 30.7 per 10,000; per-year increase was 2.3% (1.1-3.5) in 1994-2004, and per-year decrease was 3.4% (−6.6 to −0.0) in 2004-2009. Numbers included severe CHD in stillbirths and terminated pregnancies. Conclusions: The birth prevalence of CHD declined from around 2005. Specifically, the prevalence of severe CHD was reduced by 3.4% per year from 2004 through 2009. (Am Heart J 2014;168:956-64.)

• Wallace, Sean Ciaran; Døhlen, Gaute; Holmstrøm, Henrik; Lund, Christian & Russell, David (2014). Cerebral microemboli detection and differentiation during transcatheter closure of atrial septal defect in a paediatric population. Cardiology in the Young. ISSN 1047-9511. 25(2), p. 237–244. doi: 10.1017/S1047951113002072. Full text in Research Archive
• Landolt, M A; Ystrøm, Eivind; Stene-Larsen, Kim; Holmstrøm, Henrik & Vollrath, Margarete E. (2014). Exploring causal pathways of child behavior and maternal mental health in families with a child with congenital heart disease: a longitudinal study. Psychological Medicine. ISSN 0033-2917. 44(16), p. 3421–3433. doi: 10.1017/S0033291713002894. Full text in Research Archive
• Dale, Maria Teresa Grønning; Solberg, Øivind; Holmstrøm, Henrik Alf B; Landolt, Markus A; Eskedal, Leif Torvald & Vollrath, Margarete E. (2013). Well-being in mothers of children with congenital heart defects: a 3-year follow-up. Quality of Life Research. ISSN 0962-9343. 22(8), p. 2063–2072. doi: 10.1007/s11136-012-0326-0. Full text in Research Archive
• Vatne, Torun Marie; Finset, Arnstein; Ørnes, Knut; Holmstrøm, Henrik; Cvancarova, Milada S. & Ruland, Cornelia (2013). Effects of an interactive symptom communication tool for children with heart disease on patientprovider communication in outpatient care: Preliminary results. Journal of Communication in Healthcare. ISSN 1753-8068. 6(2), p. 106–114. doi: 10.1179/1753807612Y.0000000020. Full text in Research Archive
• Mitra, Souvik; Rønnestad, Arild Erlend & Holmstrøm, Henrik (2013). Management of patent ductus arteriosus in preterm infants - where do we stand? Congenital Heart Disease. ISSN 1747-079X. 8(6), p. 500–512. doi: 10.1111/chd.12143. Full text in Research Archive
• Dale, Maria Teresa Grønning; Solberg, Øivind; Holmstrøm, Henrik Alf B; Landolt, Markus A; Eskedal, Leif Torvald & Vollrath, Margarete E. (2013). Relationship Satisfaction Among Mothers of Children With Congenital Heart Defects: A Prospective Case-Cohort Study. Journal of Pediatric Psychology. ISSN 0146-8693. 38(8), p. 915–926. doi: 10.1093/jpepsy/jst038. Full text in Research Archive
• Brun, Henrik; Moller, Thomas; Freriksen, Per Morten; Thaulow, Erik; Pripp, Are Hugo & Holmstrøm, Henrik Alf B (2012). Mechanisms of Exercise-Induced Pulmonary Hypertension in Patients With Cardiac Septal Defects. Pediatric Cardiology. ISSN 0172-0643. 33(5), p. 782–790. doi: 10.1007/s00246-012-0216-9. Full text in Research Archive
• Holmstrøm, Henrik Alf B; Bjørnstad, Per G; Smevik, Bjarne & Lindberg, Harald L (2012). Balloon dilatation of pulmonary artery banding: Norwegian experience over more than 20 years. European Heart Journal. ISSN 0195-668X. 33(1), p. 61–66. doi: 10.1093/eurheartj/ehp406. Full text in Research Archive
• Dale, Maria Teresa Grønning; Solberg, Øivind; Holmstrøm, Henrik Alf B; Landolt, Markus A; Eskedal, Leif Torvald & Vollrath, Margarete E. (2012). Mothers of infants with congenital heart defects: well-being from pregnancy through the child's first six months. Quality of Life Research. ISSN 0962-9343. 21(1), p. 115–122. doi: 10.1007/s11136-011-9920-9. Full text in Research Archive
• Solberg, Øivind; Dale, Maria Teresa Grønning; Holmstrøm, Henrik Alf B; Eskedal, Leif Torvald; Landolt, Markus A. & Vollrath, Margarete E. (2012). Trajectories of Maternal Mental Health: A Prospective Study of Mothers of Infants With Congenital Heart Defects From Pregnancy to 36 Months Postpartum. Journal of Pediatric Psychology. ISSN 0146-8693. 37(6), p. 687–696. doi: 10.1093/jpepsy/jss044. Full text in Research Archive
• Brun, Henrik; Ueland, Thor; Thaulow, Erik; Damås, Jan Kristian; Yndestad, Arne & Aukrust, Pål [Show all 7 contributors for this article] (2011). No Inflammatory Response Related to Pulmonary Hemodynamics in Children with Systemic to Pulmonary Shunts. Congenital Heart Disease. ISSN 1747-079X. 6(4), p. 338–346. doi: 10.1111/j.1747-0803.2011.00505.x. Full text in Research Archive
• Solberg, Øivind; Dale, Maria Teresa Grønning; Holmstrøm, Henrik; Eskedal, Leif Torvald; Landolt, Markus A & Vollrath, Margarete E. (2011). Long-term symptoms of depression and anxiety in mothers of infants with congenital heart defects. Journal of Pediatric Psychology. ISSN 0146-8693. 36(2), p. 179–187. doi: 10.1093/jpepsy/jsq054. Full text in Research Archive
• Stene-Larsen, Kim; Brandlistuen, Ragnhild Eek; Holmstrøm, Henrik; Landolt, Markus A; Eskedal, Leif Torvald & Engdahl, Bo Lars [Show all 7 contributors for this article] (2011). Longitudinal findings from a Norwegian case-cohort study on internalizing problems in children with congenital heart defects. Acta Paediatrica. ISSN 0803-5253. 100(2), p. 236–241. doi: 10.1111/j.1651-2227.2010.02015.x. Full text in Research Archive
• Solberg, Øivind; Dale, Maria Teresa Grønning; Holmstrøm, Henrik Alf B; Eskedal, Leif Torvald; Landolt, Markus A & Vollrath, Margarete E. (2011). Emotional reactivity in infants with congenital heart defects and maternal symptoms of postnatal depression. Archives of Women's Mental Health. ISSN 1434-1816. 14(6), p. 487–492. doi: 10.1007/s00737-011-0243-1. Full text in Research Archive
• Stene-Larsen, Kim; Brandlistuen, Ragnhild Eek; Holmstrøm, Henrik Alf B; Landolt, Markus A; Eskedal, Leif Torvald & Engdahl, Bo Lars [Show all 7 contributors for this article] (2011). Longitudinal analysis of emotional problems in children with congenital heart defects: a follow-up from age 6 to 36 months. Journal of Developmental and Behavioral Pediatrics. ISSN 0196-206X. 32(6), p. 461–464. doi: 10.1097/DBP.0b013e3182202d2b. Full text in Research Archive
• Brandlistuen, Ragnhild Eek; Stene-Larsen, Kim; Holmstrøm, Henrik Alf B; Landolt, MA; Eskedal, Leif Torvald & Vollrath, Margarete E. (2011). Symptoms of communication and social impairment in toddlers with congenital heart defects. Child: Care, Health and Development. ISSN 0305-1862. 37(1), p. 37–43. doi: 10.1111/j.1365-2214.2010.01148.x. Full text in Research Archive
• Brandlistuen, Ragnhild Eek; Stene-Larsen, Kim; Holmstrøm, Henrik Alf B; Landolt, Markus A.; Eskedal, Leif Torvald & Vollrath, Margarete E. (2011). Occurrence and predictors of developmental impairments in 3-year-old children with congenital heart defects. Journal of Developmental and Behavioral Pediatrics. ISSN 0196-206X. 32(7), p. 526–532. doi: 10.1097/DBP.0b013e318222eb5a. Full text in Research Archive
• Brandlistuen, Ragnhild Eek; Stene-Larsen, Kim; Holmstrøm, Henrik Alf B; Landolt, Markus A; Eskedal, Leif Torvald & Vollrath, Margarete E. (2010). Motor and social development in 6-month-old children with congenital heart defects. Journal of Pediatrics. ISSN 0022-3476. 156(2), p. 265–269. doi: 10.1016/j.jpeds.2009.08.035. Full text in Research Archive
• Stene-Larsen, Kim; Brandlistuen, Ragnhild Eek; Holmstrøm, Henrik; Landolt, MA; Eskedal, Leif Torvald & Vollrath, Margarete E. (2010). Emotional reactivity in infants with congenital heart defects: findings from a large case-cohort study in Norway. Acta Paediatrica. ISSN 0803-5253. 99(1), p. 52–55. doi: 10.1111/j.1651-2227.2009.01515.x. Full text in Research Archive
• Møller, Thomas Friedrich; Brun, Henrik; Fredriksen, Per-Morten; Holmstrøm, Henrik Alf B; Pettersen, Eirik & Thaulow, Erik (2010). Moderate Altitude Increases Right Ventricular Pressure and Oxygen Desaturation in Adolescents with Surgically Closed Septal Defect. Congenital Heart Disease. ISSN 1747-079X. 5(6), p. 556–564. doi: 10.1111/j.1747-0803.2010.00425.x. Full text in Research Archive
• Holten-Andersen, Mads; Sulheim, Dag; Indrebø, Marianne Muller & Holmstrøm, Henrik (2010). An 11-month-year-old girl with repeated respiratory infections. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 130(8), p. 846–8. Full text in Research Archive
• Tandberg, Bente Silnes; Ystrøm, Eivind; Vollrath, Margarete E. & Holmstrøm, Henrik (2010). Feeding infants with CHD with breast milk: Norwegian Mother and Child Cohort Study. Acta Paediatrica. ISSN 0803-5253. 99(3), p. 373–378. doi: 10.1111/j.1651-2227.2009.01605.x. Full text in Research Archive
• Møller, Thomas; Brun, Henrik; Fredriksen, Per Morten; Holmstrøm, Henrik Alf B; Peersen, Kari & Pettersen, Eirik [Show all 9 contributors for this article] (2010). Right Ventricular Systolic Pressure Response During Exercise in Adolescents Born With Atrial or Ventricular Septal Defect. American Journal of Cardiology. ISSN 0002-9149. 105(11), p. 1610–1616. doi: 10.1016/j.amjcard.2010.01.024. Full text in Research Archive
• Møller, Thomas Friedrich; Leren, Trond P.; Eiklid, Kristin Louise; Holmstrøm, Henrik Alf B; Fredriksen, Per-Morten & Thaulow, Erik (2010). A novel BMPR2 gene mutation associated with exercise-induced pulmonary hypertension in septal defects. Scandinavian Cardiovascular Journal. ISSN 1401-7431. 44(6), p. 331–336. doi: 10.3109/14017431.2010.525747. Full text in Research Archive
• Brun, Henrik; Holmstrøm, Henrik Alf B; Thaulow, Erik; Damås, Jan Kristian; Yndestad, Arne & Aukrust, Pål [Show all 7 contributors for this article] (2009). Patients with Pulmonary Hypertension Related to Congenital Systemic-to-Pulmonary Shunts are Characterized by Inflammation Involving Endothelial Cell Activation and Platelet-mediated Inflammation. Congenital Heart Disease. ISSN 1747-079X. 4(1), p. 153–159. Full text in Research Archive
• Møller, Thomas; Peersen, K; Pettersen, Eirik; Thaulow, Erik; Holmstrøm, Henrik Alf B & Fredriksen, PM (2009). Non-invasive measurement of the response of right ventricular pressure to exercise, and its relation to aerobic capacity. Cardiology in the Young. ISSN 1047-9511. 13, p. 1–9. Full text in Research Archive
• Nyrnes, Siri Ann & Holmstrøm, Henrik Alf B (2007). Akutte komplikasjoner ved univentrikulære tilstander. In Klingenberg, Claus (Eds.), Veileder i akutt Pediatri. Den Norske Legeforening. ISSN 9788280700544. Full text in Research Archive
• Ruud, Ellen; Holmstrøm, Henrik Alf B; Bergan, Stein & Wesenberg, Finn (2007). Oral anticoagulation with warfarin is significantly influenced by steroids and CYP2C9 polymorphisms in children with cancer. Pediatric Blood & Cancer. ISSN 1545-5009. 48(6). doi: 10.1002/pbc.21133. Full text in Research Archive Show summary

  Clinical management of warfarin therapy is complex, and dosing algorithms do not include genetic factors or interactions with other drugs for warfarin dose determinations. We evaluated the interaction of warfarin and CYP2C9 polymorphisms and concomitant corticosteroids in 29 children with cancer. Children with heterozygous polymorphisms of CYP2C9 achieved target INR sooner and more frequently had INR above the target level, compared to children without mutations. Children on concomitant steroids had significantly lower warfarin requirements. Thus, awareness of CYP2C9 genotype and steroid-induced responsiveness to warfarin may be important when administrating oral anticoagulation in children.

• Brun, Henrik; Thaulow, Erik; Fredriksen, Per Morten & Holmstrøm, Henrik Alf B (2007). Treatment of patients with Eisenmenger's syndrome with Bosentan. Cardiology in the Young. ISSN 1047-9511. 17(3), p. 288–294. doi: 10.1017/S1047951107000522. Full text in Research Archive Show summary

  We treated prospectively 14 patients with Eisenmenger's syndrome, with a mean age of 10 years, ranging from 3 to 18 years. Treatment continued for 12 months, and demonstrated a lasting symptomatic improvement, but no improvement in terms of mean saturation of oxygen over 24 hours. Exercise capacity, as judged by peak uptake of oxygen, worsened in the six patients able to perform a treadmill test. The symptomatic benefit from dual blockage of endothelin receptors in these patients may be due to mechanisms other than selective pulmonary vasodilatation alone.

• Ruud, Ellen; Holmstrøm, Henrik Alf B; Lange, Charlotte De; Hogstad, E. M. & Wesenberg, Finn (2006). Low-dose warfarin for the prevention of central line-associated thromboses in children with malignancies--a randomized, controlled study. Acta Paediatrica. ISSN 0803-5253. 95(9), p. 1053–1059. doi: 10.1080/08035250600729092. Full text in Research Archive Show summary

  Background: Central venous lines (CVLs) are essential in the care of children with malignancies, but are associated with venous thromboembolism (VTE) and infections. Effective and safe prophylactic approaches are deficient. Aim: To perform a study of adjusted low-dose warfarin for the prevention of CVL-related VTE in children with malignancies. Methods: Children with newly diagnosed cancer, a CVL in a jugular vein and an expected treatment period of over 6 mo were eligible for the study. Participants were randomized to low-dose warfarin, with intended international normalized ratio (INR) 1.3–1.9, or to a control group. Primary outcome was VTE in a jugular vein diagnosed by ultrasonography at 1, 3 and 6 mo after inclusion. Secondary outcome was CVL-related infections, mainly measured as days on antibiotics or positive blood cultures. Results: The study enrolled 73 children, and 62 completed it fully. Asymptomatic CVL-related VTE was frequent (42%), but often transient. Regardless of severity, timing and duration, CVL-related VTE was equally frequent among children on warfarin as compared to controls (p=0.44). Low-dose warfarin (p=0.59) or jugular CVL-related VTE (p=0.91) did not have any impact on days on antibiotics, but we observed a tendency towards an association between CVL-related VTE and positive blood cultures (p=0.15). Conclusion: Our randomized study of low-dose oral anticoagulation for the prevention of CVL-related asymptomatic VTE in children with cancer did not show any benefit of warfarin adjusted to maintain INR between 1.3 and 1.9.

• Ruud, Ellen; Holmstrøm, Henrik Alf B; Hopp, Einar & Wesenberg, Finn (2006). Central line-associated venous late effects in children without prior history of thrombosis. Acta Paediatrica. ISSN 0803-5253. 95(9), p. 1060–1065. doi: 10.1080/08035250500499457. Full text in Research Archive Show summary

  Background: The frequency of asymptomatic central line-associated thromboses is high and well recognized among children with cancer, while the long-term consequences are mainly unknown. Aim: In a cross-sectional study, we evaluated clinical and radiological venous outcome in children with previous long-standing intravascular catheters. Methods: The study enrolled 71 children previously treated for malignant or haematological diseases, 4–180 (median 37) mo after removal of their central lines. Inclusion criteria were a prior central line in a jugular vein for a minimum of 6 mo and no previous history of thrombosis. The children had clinical examination for post-thrombotic syndrome (PTS) and Doppler ultrasonography of the central neck veins. Twelve children had additional venous magnetic resonance imaging (MRI). But no kind of venography was performed in the remaining. Results: We observed mild PTS with increased superficial collaterals in four children (6%), but no cases of more severe PTS. None complained of symptoms related to venous late effects. By ultrasonography, post-thrombotic venous alterations were detected in 17 children (24%), and five of these had complete occlusion of the veins. The sensitivity for pathologically increased collaterals to identify occlusive thrombosis was 0.6, while the specificity was 0.98. Occlusive venous thromboembolism was associated with the total number of central venous lines (CVLs; p=0.002), previous severe CVL-associated infections (p=0.001) and duration of central line in place (p=0.042). Conclusion: In spite of no prior history of thrombosis, children with previous long-term jugular lines frequently had local thrombotic sequelae, while clinical symptoms of PTS were rare

• Ruud, Ellen; Holmstrøm, Henrik Alf B; Brosstad, Frank Roger & Wesenberg, Finn (2006). Children with acute lymphoblastic leukaemia have high plasma levels of total homocysteine at time of diagnosis. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 66(1), p. 67–78. Full text in Research Archive Show summary

  Objective. Cancer can induce venous thromboembolic complications for various reasons. As part of a greater study, acquired and congenital prothrombotic risk factors were investigated in children with leukaemia or non-Hodgkin's lymphoma and compared with similar investigations in children with congenital heart defects. Material and methods. Blood samples were taken from 60 children with newly diagnosed leukaemia or lymphoma and 133 children with congenital heart defects in the course of a scheduled cardiac catheterization. When children with cancer were in remission, analyses of acquired prothrombotic risk factors were repeated. Children with cancer were observed for symptoms of thromboembolism throughout their treatment period. Results. Total homocysteine levels were significantly raised in children with cancer (median value 10.0 micromol/L) as compared with the levels in children with congenital heart diseases (5.0 micromol/L) (p<0.001), while children with acute lymphoblastic leukaemia had the highest values. The median level of lipoprotein(a) was slightly increased in children with newly diagnosed leukaemia or lymphoma (105 mg/L versus 100 mg/L, p<0.001), and levels of coagulation inhibitors were higher (p<0.001). Total homocysteine levels normalized when children attained remission of cancer disease. Two children had symptoms of acute thrombosis. Conclusions. Raised concentrations of total homocysteine were frequent in children with newly diagnosed cancer, but this normalized when the children were in remission. The clinical significance of our observations and the impact on venous thromboembolism have yet to be defined.

• Ruud, Ellen; Holmstrøm, Henrik Alf B; Lange, Charlotte De; Natvig, Solveig; Albertsen, B.K. & Wesenberg, Finn (2006). THROMBOTIC EFFECTS OF ASPARAGINASE IN TWO ACUTE LYMPHOBLASTIC LEUKEMIA PROTOCOLS (NOPHO ALL-1992 VERSUS NOPHO ALL-2000): A Single-Institution Study. Pediatric Hematology & Oncology. ISSN 0888-0018. 23(3), p. 207–216. doi: 10.1080/08880010500506701. Full text in Research Archive Show summary

  Asparaginase is essential in the treatment of lymphoproliferative malignancies, but it is associated with several side effects. The objective of this study was to compare asparaginase-induced alterations of the coagulation inhibitors and the impact on central line-associated thrombosis in children treated according to 2 different asparaginase regimens. The study enrolled 30 children treated for acute lymphoblastic leukemia, and they were divided into 2 groups with respect to asparaginase preparation and protocol (NOPHO ALL-1992 versus NOPHO ALL-2000). The coagulation inhibitors antithrombin, protein C, and proteins S were measured prior to and during asparaginase therapy, and incidence of central line-associated thromboses was compared to evaluate the protocols' thrombogenicity. Thirteen children received Erwinia asparaginase and 17 children received E. coli asparaginase. Independent of protocol, the coagulation inhibitors were significantly reduced during asparaginase therapy (p < .001), and central line-associated thromboses were frequent. Four children developed thrombosis in the course of asparaginase therapy, and there was a correlation between asparaginase-induced fall of antithrombin and occurrence of new thromboses (p = .01).

• Ruud, Ellen; Holmstrøm, Henrik Alf B; Brosstad, Frank Roger & Wesenberg, Finn (2005). Diagnostic value of family histories of thrombosis to identify children with thrombophilia. Pediatric Hematology & Oncology. ISSN 0888-0018. 22(6), p. 453–462. Full text in Research Archive Show summary

  Thrombophilia screening is a time-consuming and expensive procedure. Information about thromboembolism among relatives may be a simple method to identify those at risk of having thrombophilia. In a cross-sectional clinical study the authors have investigated the role of such family histories to detect children with thrombophilia. In 202 children a family history of venous or arterial thromboembolism was recorded. The participants were either children with congenital heart defects at the time of a scheduled cardiac catheterization (n=134) or children with newly diagnosed cancer (n=68). Questions were answered, on the spot, by the parents, at the same time as blood samples for thrombophilia screening were taken. Questions about family history of thromboembolism were completed in 184 children, of whom 114 children (62%) were positive, and 35 of these had relatives with venous thromboembolic events. Only one child had an affected first-degree relative. Thrombophilic alterations were observed in 60 children (30%), and 25 of these were defined as inherited. A positive family history of venous origin increased the relative risk of a child having inherited thrombophilia to 2.35 (95% confidence interval 1.1--5.2). Information about familial arterial thromboembolism was not useful in spotting children with prothrombotic risk factors. These results indicate that questioning about family history of venous thromboembolism may identify children with genetic thrombophilia, but the association is not strong. The authors encourage similar larger-scale studies to enlighten the issue fully

• Brun, Henrik; Holmstrøm, Henrik Alf B & Thaulow, Erik (2005). Sudden death during a change in treatment for pulmonary hypertension. Cardiology in the Young. ISSN 1047-9511. 15(2), p. 223–225. Full text in Research Archive Show summary

  We describe an infant with an atrioventricular septal defect and separate valvar orifices for the right and left ventricles, the so-called primum defect, who presented with serious pulmonary hypertension. Treatment with sildenafil was changed to intravenous epoprostenol due to lack of any measurable effects of the initial therapy as shown by echocardiography. The girl died three days after the change in treatment. We suggest that a mismatch between ventilation and perfusion contributed significantly to her death

• Brun, Henrik; Holmstrøm, Henrik Alf B; Greve, G & Thaulow, Erik (2004). Pulmonal hypertensjon hos barn (del 1). Hjerteforum. ISSN 0802-1465. 16, p. 35–44. Full text in Research Archive
• Brun, Henrik; Holmstrøm, Henrik Alf B; Greve, G & Thaulow, Erik (2004). Pulmonal hypertensjon hos barn (del 2). Hjerteforum. ISSN 0802-1465. 17, p. 36–45. Full text in Research Archive
• Ruud, Ellen; Holmstrøm, Henrik; Aagenaes, I; Hafsahl, Geir; Handeland, Martin & Kyte, A [Show all 7 contributors for this article] (2003). Successful thrombolysis by prolonged low-dose alteplase in catheter-directed infusion. Acta Paediatrica. ISSN 0803-5253. 92(8), p. 973–6. Full text in Research Archive
• Bjørnstad, Per G; Holmstrøm, Henrik; Smevik, Bjarne & et, al. (2003). Transcatheter closure of atrial septal defects in the oval fossa. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 123(15), p. 2052–4. Full text in Research Archive

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• Sekkelsten, Anna Irene Skei; Skattør, Thor Håkon; Holmstrøm, Henrik; Krohg-Sørensen, Kirsten & Paus, Benedicte (2025). Vascular findings in five unrelated children with vascular Ehlers-Danlos syndrome: A multi-case report. doi: 10.1016/j.ejmg.2025.105035. Full text in Research Archive Show summary

  Abstract Vascular Ehlers-Danlos syndrome (vEDS) is an inherited connective tissue disorder caused by heterozygous variants in COL3A1, leading to tissue and vessel fragility alongside an increased risk of potentially fatal aneurysms and dissections. Although vascular events most commonly manifest in adulthood, childhood events also occur. Knowledge on clinical manifestations in childhood and potential benefits of vascular surveillance is limited, and no evidence-based guidelines for predictive genetic testing and follow-up exist. We present five patients diagnosed with vEDS in childhood, focusing on vascular events. The patients receive follow-up at a multidisciplinary heritable thoracic aortic disease clinic at Oslo University Hospital and are registered in the associated patient registry. Two of the five patients experienced a childhood vascular event, both involving cerebral vessels. In one of these patients, the event may not be vEDS related. A mild aortic root dilatation was detected in one patient. No severe aortic events like dissection or rupture were reported in childhood, but one patient died from an aortic dissection in early adulthood despite normal findings on MRA scans in the years he received regular surveillance. Our findings highlight the variable expressivity of vEDS, including severe childhood vascular events. Further studies to evaluate the effect of surveillance are needed to form an evidence base for surveillance guidelines in pediatric patients. Established benefits of surveillance and management are essential for deciding on whether and when to perform predictive genetic testing of a child at risk.

• Brekke, Idunn; Vedeler, Janikke Solstad; Früh, Elena Albertini; Alecu, Andreea I.; Anvik, Cecilie Høj & Austgulen, Marthe Hårvik [Show all 19 contributors for this article] (2024). Svikter velferdsstaten kvinner? Fontene. ISSN 0805-5432. Full text in Research Archive
• Dalen, Marit Lunde; Vigerust, Natalya Filipchuk; Hammarström, Clara Louise; Holmstrøm, Henrik & Andresen, Jannicke Hanne (2022). Neonatal interstitial lung disease in a girl with Jacobsen syndrome: a case report. Journal of Medical Case Reports. 16, p. 1–6. doi: 10.1186/s13256-022-03351-5. Full text in Research Archive Show summary

  Background We report a case of the neonatal interstitial lung disease pulmonary interstitial glycogenosis in a girl with Jacobsen syndrome. While Jacobsen syndrome is caused by a deletion on the long arm of chromosome 11 and is genetically confirmed, pulmonary interstitial glycogenosis is of unknown etiology and is diagnosed by lung biopsy. Pulmonary interstitial glycogenosis has not previously been described in association with Jacobsen syndrome. Case presentation A term newborn small for gestational age Caucasian girl presented with respiratory distress, pulmonary hypertension, congenital heart defects, immunodeficiency, and thrombocytopenia. She was diagnosed with Jacobsen syndrome, but also had pulmonary interstitial glycogenosis, which contributed to significant morbidity. There was striking clinical improvement after steroid treatment of the pulmonary interstitial glycogenosis. Conclusions Interstitial lung disease should be considered as a differential diagnosis when respiratory distress and hypoxemia in the perinatal period worsens or persists despite standard treatment. Importantly, pulmonary interstitial glycogenosis may be treatable with corticosteroids. Whether there is a genetic link between pulmonary interstitial glycogenosis and Jacobsen syndrome is still unknown.

• Hjorth-Johansen, Elin; Holmstrøm, Henrik; Børøsund, Elin; Moen, Anne; Eger, Siw Helen Westby & Wik, Gunnar [Show all 8 contributors for this article] (2022). A mobile application to support parents of infants with severe cardiac disease. Full text in Research Archive
• Lee, Anja & Holmstrøm, Henrik (2019). N?r barn ikke skal bli gamle. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 139(7). doi: 10.4045/tidsskr.19.0210. Full text in Research Archive
• Øyen, Anne-Siri; Ulleberg, Bente; Sangar, Paul; Wallace, Sean Ciaran & Holmstrøm, Henrik (2018). A-S. Øyen og medarbeidere svarer. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 138(1), p. 16–16. doi: 10.4045/tidsskr.17.1091. Full text in Research Archive
• Vollrath, Margarete E.; Stene-Larsen, Kim; Brandlistuen, Ragnhild Eek; Holmstrøm, Henrik Alf B; Eskedal, Leif Torvald & Landolt, Markus A. (2013). Internalizing and externalizing problems in children with congenital heart disease. Full text in Research Archive
• Stene-Larsen, Kim; Solberg, Øivind; Vollrath, Margarete E.; Holmstrøm, Henrik; Eskedal, Leif Torvald & Landolt, MA [Show all 8 contributors for this article] (2009). HEARTKIDS og HEARTMOMS: to store prosjekter om medfødt hjertefeil og psykisk helse ved Nasjonalt folkehelseinstitutt. Full text in Research Archive
• Holmstrøm, Henrik Alf B & Thaulow, Erik (2005). Ekko for alle barn med bilyd? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 125(8), p. 994–994. Full text in Research Archive Show summary

  Klinisk undersøkelse av barn med hjertefeil har høy treffsikkerhet, men er den god nok?

• Brun, Henrik; Holmstrøm, Henrik Alf B; Fredriksen, Per Morten; Matthews, Iren; Lund, May Brit & Thaulow, Erik (2005). Behandlingsprogram ved Eisenmenger-syndrom- hvordan måle effekt? Paidos: Tidsskrift for Norsk barnelegeforening. ISSN 1503-5360. p. 10–10. Full text in Research Archive Show summary

  Abstrakt fra Norsk Barnelegeforenings høstmøte 2004

• Holmstrøm, Henrik Alf B (2005). Orphan drugs and off-license use � drug treatment in congenital heart disease as a case in point. Full text in Research Archive
• Dale, Maria Teresa Grønning; Vollrath, Margarete E. & Holmstrøm, Henrik Alf B (2012). Well-being among mothers of children with congenital heart defects: a prospective case-cohort study from pregnancy to 36 months after delivery. Universitetet i Oslo. Full text in Research Archive
• Stene-Larsen, Kim; Vollrath, Margarete E. & Holmstrøm, Henrik Alf B (2011). Emotional and behavioral problems in infants and toddlers with congenital heart defects. A longitudinal study from birth to 36 months of age. Unipub forlag. Full text in Research Archive

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