Ketil Størdal

• Kvenshagen, Line Norman; Kvenshagen, Hanna Norman; Holte, Kari; Jacobsen, Anne Flem; Størdal, Ketil & Hubin, Aliaksandr [Show all 7 contributors for this article] (2026). Association between Regional Labour Analgesia and Neonatal Heart Rate Immediately after Birth. Neonatology. ISSN 1661-7800. p. 1–8. doi: 10.1159/000550615.
• Sigvardsson, Ida; Ludvigsson, Johnny; Lerchova, Tereza; Imberg, Henrik; Størdal, Ketil & Mårild, Karl Staffan (2026). Timing of complementary food introduction is not associated with inflammatory bowel disease risk: A prospective birth cohort study. Inflammatory Bowel Diseases. ISSN 1078-0998. 32(10), p. 1937–1948. doi: 10.1093/ibd/izag093. Full text in Research Archive
• Sigvardsson, Ida; Størdal, Ketil; Imberg, Henrik; Fernell, Elisabeth; Gillberg, Christopher & Ludvigsson, Johnny [Show all 7 contributors for this article] (2026). Early-life adverse events and risk of inflammatory bowel disease: A Scandinavian birth cohort study. Journal of Pediatric Gastroenterology and Nutrition - JPGN. ISSN 0277-2116. doi: 10.1002/jpn3.70537. Full text in Research Archive
• Guo, Annie; Sigvardsson, Ida; Imberg, Henrik; Lerchova, Tereza; Ludvigsson, Johnny & Størdal, Ketil [Show all 7 contributors for this article] (2026). Modifiable lifestyle factors in early life and inflammatory bowel disease risk in two birth cohorts. Journal of Crohn's and Colitis. ISSN 1873-9946. 20(8), p. 1–12. doi: 10.1093/ecco-jcc/jjag114. Full text in Research Archive
• Östman, Maria Linn Olivia; Størdal, Ketil; Tapia, German & Stene, Lars Christian Mørch (2026). Rotavirus vaccination and incidence of type 1 diabetes: a population-based natural experiment. Diabetologia. ISSN 0012-186X. doi: 10.1007/s00125-026-06832-0. Full text in Research Archive Show summary

  Aims/hypothesis Environmental factors, including infections, have been suspected to influence the risk of type 1 diabetes. Studies of rotavirus vaccine and risk of type 1 diabetes have shown conflicting results. We took advantage of the rapid and high uptake of the rotavirus vaccine among infants in Norway as a natural experiment to study the potential association between rotavirus vaccination and type 1 diabetes incidence in Norway. Methods In this cohort study, we followed all children born in Norway during 2007–2019 from 6 months to 5 years of age for type 1 diabetes. In an interrupted time series analysis, we compared type 1 diabetes incidence in children born before compared with after introduction of the rotavirus vaccination programme in September 2014. Results Of 740,744 included children, 846 were diagnosed with type 1 diabetes between 6 months and 5 years of age. Our primary interrupted time series analysis showed an increasing trend after implementation of the rotavirus vaccination programme (relative HR 1.11 [95% CI 1.03, 1.20]), which was not significant after excluding birth cohorts from 2013–2015 to avoid potential herd immunity effects (relative HR 1.05 [95% CI 0.93, 1.18]). In a secondary analysis comparing fully vaccinated with non-vaccinated children, the adjusted HR was 1.17 (95% CI 0.78, 1.77). Conclusions/Interpretation This study found no evidence for a reduced risk of type 1 diabetes after introduction of rotavirus vaccination in infancy.

• Mattila, Markus; Tapia, German; Størdal, Ketil; Brantsæter, Anne Lise; Virtanen, Suvi M. & Lund-Blix, Nicolai Andre [Show all 133 contributors for this article] (2026). Maternal Intake of Vitamins A, C, D, and E During Pregnancy and Risk of Type 1 Diabetes in the Child: The Norwegian Mother, Father, and Child Cohort Study. American Journal of Clinical Nutrition. ISSN 0002-9165. 124(3). doi: 10.1016/j.ajcnut.2026.101431. Full text in Research Archive
• Dåstøl, Vilde Øverlien; Caspersen, Ida Henriette; Haftorn, Kristine Løkås; Hestetun, Sigrid Valen; Bastakoti, Srijana & Andreassen, Ole [Show all 11 contributors for this article] (2026). Maternal weight and hypertension as risk factors for juvenile idiopathic arthritis: a prospective population-based pregnancy cohort study. RMD Open. 12(3). doi: 10.1136/rmdopen-2026-006940. Full text in Research Archive Show summary

  Objectives: The intrauterine environment may influence childhood immune-mediated disease risk. We investigated whether maternal prepregnancy body mass index (BMI), gestational weight gain (GWG) or hypertensive disorders during pregnancy (HDP) were associated with juvenile idiopathic arthritis (JIA) in children and whether genetic susceptibility modified associations. Methods: We linked the Norwegian Mother, Father and Child Cohort Study (MoBa) to the Norwegian Patient Registry to identify children with JIA. Logistic regression estimated adjusted ORs (aORs) for associations with BMI, GWG and HDPs. Causal mediation analyses assessed whether hypertension mediated the GWG–JIA association. In a genotyped subsample, we tested interactions between exposures and a JIA Polygenic Risk Score (PRS). Results: Among 78 901 eligible children, 265 developed JIA (genotyped subsample: 192 JIA/44 053 non-JIA). By the end of follow-up, all children were ≥14 years old and 85% were ≥16 years old. Maternal prepregnancy BMI was not associated with JIA. Each 1 SD (~6 kg) increase in GWG was associated with modestly higher odds of JIA (aOR 1.12, 95% CI 1.00 to 1.26), particularly among women with prepregnancy obesity (aOR 1.40, 95% CI 1.10 to 1.77). Maternal hypertension and pre-eclampsia were associated with higher JIA risk (aOR 1.43, 95% CI 1.02 to 1.99 and aOR 1.61, 95% CI 1.10 to 2.37). Hypertension did not mediate the GWG–JIA association (p>0.05). Among children with lower PRS, maternal obesity was associated with a lower JIA risk (aOR 0.37, 95% CI 0.17 to 0.80). Conclusion: Higher GWG and HDPs were independently associated with increased JIA risk. Genetic susceptibility may modify associations with maternal BMI, supporting a role for pregnancy health in JIA development.

• Øymar, Knut Asbjørn Alexander; Selvakumar, Joel Pradeepkumar; Øymar, Maren Våland; Dalen, Ingvild; Klaseie, Ken Erik & SIVANANTHAM, UJINTHINI [Show all 12 contributors for this article] (2026). High-Flow Nasal Cannula and Continuous Positive Airway Pressure in Infants With Acute Bronchiolitis—Trends of Use in Norway. Acta Paediatrica. ISSN 0803-5253. doi: 10.1111/apa.70643. Full text in Research Archive
• Segerstad, Elin Malmberg Hård af; Thesen, Mari; Tapia, German; Brantsæter, Anne Lise; Parr, Christine Louise & Magnus, Maria Christine [Show all 9 contributors for this article] (2026). Early life intake of marine n-3 fatty acids, genetic fatty acid desaturase variants, and risk of celiac disease. American Journal of Gastroenterology. ISSN 0002-9270. doi: 10.14309/ajg.0000000000004012. Full text in Research Archive Show summary

  INTRODUCTION: We aimed to investigate whether early-life marine n-3 fatty acids and fish intake, and fatty acid desaturase (FADS) genetic variants were associated with later risk of celiac disease (CeD). METHODS: Among 85,244 children in the prospective Norwegian Mother, Father, and Child Cohort Study, fish and marine fatty acid intakes were estimated from questionnaires to mothers during pregnancy, and at child's age 6 and 18 months. rs1535 tagged common FADS haplotypes. Child's CeD status was obtained from the Norwegian Patient Registry and parental questionnaires. RESULTS: A total of 1,363 (1.6%) children were diagnosed with CeD (follow-up median 16.1 years; range 12.5–19.8). Total pregnancy eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake was not associated with child CeD risk (adjusted odds ratio [aOR] 1.02, 95% confidence interval [CI] = 0.94–1.10, per g/d increase). Pregnancy EPA and DHA supplementation was associated with a higher child CeD risk (aOR 1.24, 95% CI = 1.09–1.41, compared with nonuse). EPA and DHA supplementation at age 6 months (aOR 0.98, 95% CI = 0.87–1.10) and 18 months (aOR 0.98, 95% CI = 0.86–1.12), and fish intake at age 18 months (aOR 1.00, 95% CI = 0.95–1.05, per serving/week) were not associated with CeD. CeD risk was higher in children carrying FADS major alleles (OR 1.10, 95% CI = 1.00–1.20, per additional allele). DISCUSSION: Overall, there was no evidence that the total intake of marine n-3 fatty acids in early life was associated with a lower risk of CeD. Instead, data suggested an association in the positive direction for the child's genotypes resulting in higher EPA and DHA status, and EPA and DHA supplements during pregnancy, with child CeD risk.

• Størdal, Ketil; Almaas, Runar; Sanner, Helga; Sletner, Line & Stene, Lars Christian Mørch (2026). Incidence and co-occurrence of six autoimmune diseases in childhood: a population-based cohort study in Norway. The Lancet Child and Adolescent Health. ISSN 2352-4642. 10(6), p. 429–437. doi: 10.1016/S2352-4642(26)00008-8. Full text in Research Archive
• Brändle, Gabriel; Orfanos, Ioannis; Mari, Judit; Montemaggi, Alessandra; Størdal, Ketil & Trapani, Sandra [Show all 7 contributors for this article] (2026). An Opinion on Medical Overuse in the Context of the European Academy of Paediatrics Choosing Wisely Initiative. Acta Paediatrica. ISSN 0803-5253. doi: 10.1111/apa.70545. Full text in Research Archive
• Rantala, Aino K; Hakola, Leena; Brustad, Nicklas; Tapia, German; Segerstad, Elin M Hård Af & Lehtonen, Jussi [Show all 20 contributors for this article] (2026). Marine n–3 Long-Chain Polyunsaturated Fatty Acid Intake in Pregnancy and Risk of Early Life Infections in 3 Nordic Cohorts: A HEDIMED Consortium Study. Journal of Nutrition. ISSN 0022-3166. 156. doi: 10.1016/j.tjnut.2026.101456. Full text in Research Archive
• Larsen, Vilde Bergstad; Gunnes, Nina; Gran, Jon Michael; Dahl, Jesper; Bøås, Håkon & Watle, Sara Sofie Viksmoen [Show all 13 contributors for this article] (2026). Adverse events following SARS-CoV-2 mRNA vaccination in norwegian adolescents. Scientific Reports. doi: 10.1038/s41598-026-45261-2. Full text in Research Archive Show summary

  The Norwegian COVID-19 vaccination campaign of adolescents from April 2021 necessitated surveillance of potential adverse events following immunization (AEFI). In this nationwide study of 496,432 adolescents, AEFI incidence rate ratios (IRRs) after first- and second-dose SARS-CoV-2 mRNA vaccination were compared to IRRs in unvaccinated subjects, and a self-controlled case series analysis was done as a secondary analysis. Seventeen pre-selected potential AEFIs were investigated: Anaphylactic reaction, Acute appendicitis, Lymphadenopathy, Arrhythmia, Cerebrovascular events, Death, Encephalomyelitis and meningitis, Epilepsy and convulsions, Facial nerve palsy, Herpes zoster, Idiopathic thrombocytopenic purpura, Myocarditis and pericarditis, Venous thromboembolic events, Arthropathy, Guillain-Barré syndrome, IgA vasculitis, and Multisystem inflammatory syndrome in children. Most AEFI were rare among adolescents, with few cases, and there was no statistically significant increase in the incidence of AEFIs after first-dose vaccination. Increased IRRs of anaphylactic reaction, lymphadenopathy, appendicitis, and myocarditis and pericarditis were observed following second-dose vaccination.

• Størdal, Ketil; Andersen, Svend; Mårild, Karl; Larsson, Vilhelm & Imberg, Henrik (2026). Systematic review and meta-analysis of childhood exposure to antibiotics and the subsequent risk of IBD. Inflammatory Bowel Diseases. ISSN 1078-0998. doi: 10.1093/ibd/izaf324. Full text in Research Archive Show summary

  Abstract Background Antibiotic use in early childhood may alter the developing microbiome and has been proposed as a risk factor for inflammatory bowel disease (IBD). We conducted a systematic review to examine the association between childhood antibiotic use and subsequent risk of IBD. Methods In a systematic literature search, we identified cohort and case-control studies reporting the association between antibiotic use (exposure age <1 to 17 years) and development of IBD. MEDLINE and EMBASE databases were searched from inception through December 31, 2024. Studies reporting a hazard ratio, odds ratio, or risk ratio (RR) were included. To account for heterogeneity, pooled estimates were calculated using the DerSimonian-Laird random-effects model. Estimates were adjusted for potential confounding as reported in the original studies. Results We identified 10 studies, of which 8 (n = 2783 cases) reported associations between childhood antibiotics and IBD risk. Additionally, 2 studies on Crohn’s disease (CD) and 1 on ulcerative colitis were included in disease-specific analyses. In pooled analyses, antibiotic exposure compared with no exposure was associated with increased risk of IBD (RR, 1.42; 95% confidence interval [CI], 1.23-1.66), CD (RR, 1.59; 95% CI, 1.39-1.81), and ulcerative colitis (RR, 1.23; 95% CI, 1.08-1.40). Heterogeneity was low to moderate (I2 = 0%-35%), and funnel plots did not indicate publication bias (Egger’s test, P = .12-.43). Adjustment for infections did not attenuate the association between childhood antibiotic exposure and IBD development. Conclusions While causal interpretation should be cautious, childhood exposure to antibiotics was associated with an increased risk of later IBD, particularly for CD.

• Ersdal, Mia Elida Larsen; Størdal, Ketil; Munyaw, Yuda; Mdoe, Paschal Francis; Mduma, Estomih & Ersdal, Hege Langli [Show all 7 contributors for this article] (2025). Durations of first and second stage of labour and perinatal outcome. Early Human Development. ISSN 0378-3782. 209. doi: 10.1016/j.earlhumdev.2025.106340. Full text in Research Archive Show summary

  Objective To investigate the duration of active first and second stage of labour, specifically the new alert values recommended by the World Health Organisation in 2018, in relation to intrapartum stillbirths and 24-h newborn outcome (i.e. 24-h perinatal outcome). Methods A prospective observational study including deliveries at Haydom Lutheran Hospital in rural Tanzania between March 2013 through November 2018. Information about labour, delivery and newborn characteristics/outcome was recorded on data collection forms by trained data collectors, observing every delivery. Of 22,199 deliveries 12,481 were included. Exclusion criteria were: missing time variables, caesarean section, multiples and antepartum stillbirths. Logistic regression was used to model whether duration of labour was associated with risk of adverse outcome. Our main outcome measure was 24-h perinatal outcome. Results 24-h postpartum, 454 (3.6 %) newborns were dead (intrapartum stillbirths n = 118, newborn deaths n = 63) or admitted to Neonatal Unit (n = 273). Duration of first stage was categorised: <6 (n = 900), 6- < 12 (n = 9204), and ≥ 12 h (n = 2377), with no significant relation to adverse perinatal outcome for either group (p = 0.431). Duration of second stage was categorised: <1 (n = 12,342) and ≥ 1 h (n = 139). Duration ≥1 h was associated with adverse perinatal outcome, OR 3.38 (95 % CI 1.95–5.88) when adjusted for foetal heart rate during labour and before delivery, gestational age and birth weight. Conclusions Duration of first stage was not associated with adverse outcome. Second stage ≥1 h was associated with adverse outcome by more than a three-fold. Our findings are not in accordance with the new recommendations from the World Health Organisation.

• Thomassen, Rut Anne; Kvammen, Janne Anita; Bentsen, Beint Sigmund; Bratlie, Marianne; Bøhn, Siv Kjølsrud & Farstad, Hanne [Show all 15 contributors for this article] (2025). Improving well-being in children with intestinal failure: Impact of Prebiotics on Gastrointestinal Symptoms and Quality of Life, A Randomized Study. Intestinal Failure. 6(Supplement 1). doi: 10.1016/j.intf.2025.100242. Full text in Research Archive Show summary

  Background: Children with intestinal failure (IF) experience a high burden of illness, characterized by persistent gastrointestinal (GI) symptoms, irregular stool patterns, and reduced health-related quality of life (HRQOL). This study explored the impact of prebiotic supplementation on GI symptoms and HRQOL. Methods: An open-label randomized controlled trial with two phases. In Phase 1, children aged 1–18 years with IF received supplementation with a prebiotic blend for four weeks. In Phase 2, participants were randomized to either continue supplementation (intervention group) or cease supplementation (control group) for six months to evaluate long-term effects. Primary endpoints were GI symptoms and HRQOL, evaluated using PedsQL™ scales. Secondary endpoints included stool consistency and frequency, nutritional support, and antibiotic use. A paired t-test assessed short-term effect, while ANCOVA tested long-term differences. Results: Forty-seven children completed Phase 1. Of the 33 reporting on GI symptoms, 20 (60%) improved after short-term prebiotic supplementation. In Phase 2, 43 were randomized to intervention group (n=24) or control group (n=19). The intervention group exhibited significant improvements in GI symptoms compared to controls (mean difference 6.9, p=0.01). Furthermore, stool frequency decreased (median -1.0 vs. 0 stools/day, p=0.003) more in the intervention group, and stool consistency normalized more often (42% vs. 6%, p=0.02). No significant differences were observed in HRQOL scores, nutritional support, or antibiotic use. Conclusions: Although HRQOL did not improve, both short- and long-term prebiotic supplementation significantly improved GI symptoms, stool frequency, and stool consistency in children with IF, suggesting its potential as a therapeutic option in pediatric IF.

• Mäkinen, Jani; Heikkilä, Paula; Pajula, Juha; Mekkaoui, Khaoula El; Størdal, Ketil & Lindfors, Katri [Show all 13 contributors for this article] (2025). Screening for Celiac Disease in Childhood: Cost-effectiveness of Multiple Genetic and Serological Testing Approaches. Clinical Gastroenterology and Hepatology. ISSN 1542-3565. p. 1–11. doi: 10.1016/j.cgh.2025.11.030. Full text in Research Archive Show summary

  Background & Aims Celiac disease is severely underdiagnosed, and many identified patients suffer from a long diagnostic delay. Population-based screening could improve this under-recognition, but its practical implementation remains unclear. We studied the most cost-effective screening strategy for celiac disease in childhood. Methods A Markov model using primarily Swedish data was developed for comparing the cost-effectiveness of various scenarios. Key considerations included serological testing across ages 3 to 18 years, single-time vs repeated screening, and preliminary genetic testing to identify the at-risk population. Outcomes of the resulting 272 strategies were compared against a no-screening alternative using the incremental cost-effectiveness ratio. Sensitivity analysis was conducted at a €20,000 willingness to pay threshold to determine key factors influencing the optimal screening age(s) and conditions where repeated screening would be preferred. Results Untargeted single-time screening was more cost-effective than repeated screening or the combined use of genetic testing in the default scenario. Single-time screening was most cost-effective at age 11 (95% confidence interval, 10–14 years), and repeated screening at ages 4 and 11. Repeated screening was preferred if prevalence of celiac disease at age 12 was ≥5%, diagnosis improved quality of life for asymptomatic patients, screening costs were halved, or a willingness to pay of €50,000 per quality-adjusted life year was adopted. Diagnostic delay was the key factor influencing the optimal screening age(s). Conclusions The most cost-effective screening strategy for celiac disease was single-time untargeted serological testing at age 11. The optimal approach is affected by regional factors and may evolve with new evidence. Repeated screening may be preferable for high-risk groups and with high willingness to pay.

• Juma, Damas; Størdal, Ketil; Kamala, Benjamin; Bishanga, Dunstan R.; Kalolo, Albino & Moshiro, Robert Deogratias [Show all 9 contributors for this article] (2025). Changes in Health Facility Readiness for Providing Quality Maternal and Newborn Care After Implementing the Safer Births Bundle of Care Package in Five Regions of Tanzania. Healthcare. 13(23). doi: 10.3390/healthcare13233060. Full text in Research Archive Show summary

  Background: Maternal and newborn morbidity and mortality remain a pressing challenge with uneven progress globally and in Tanzania. The capacity of health facilities to provide quality care is critical to improving outcomes. This study aimed to assess changes in health facilities’ readiness to provide quality maternal and newborn care, and hence aimed to inform improvements in quality-of-care interventions in Tanzania. Methods: A before and after assessment of 28 comprehensive emergency obstetric and newborn care health facilities implementing the Safer Births Bundle of Care package in five regions of Tanzania was carried out in December 2020 and January 2023. We adapted the World Health Organization’s Service Availability and Readiness Assessment tool, which covered amenities, equipment, staff, guidelines, medicines, and diagnostic facilities. Composite readiness scores were calculated for each category and results were compared at the health facility level. For categorical variables, we tested for differences by Fisher’s exact test; for readiness scores, differences were tested by linear fixed and mixed model analyses, considering dependencies within the regions. We used p < 0.05 as our level of significance and measured change from baseline using a paired t-test. Results: The overall readiness improved significantly from 67.6% to 83.7% (p < 0.05). Statistically significant improvements were seen in medical equipment (77.1% to 94.0%), diagnostic/treatment commodities (69.3% to 83.1%), and availability of guidelines (50.8% to 96.7%). Changes in amenities (78.1% to 84.2%) and staff (63.0% to 61.7%) were not significant. The overall readiness improved in all facility types and the change was statistically significant in district hospitals and health centres (p < 0.05). There were significant differences in improvement between regions (p < 0.05) Conclusions: The overall readiness has improved significantly, reflecting a positive change. However, there remains a need for further enhancement, particularly in terms of staffing, to ensure high-quality maternal and newborn care. Authorities should take swift action to address the identified gaps, selecting the most effective and practical interventions while closely monitoring progress in readiness and sustaining the gains.

• Holte, Kari; Trovi, Cecilie Ramstad; Lie, Charlotte Fange; Grøvslien, Anne; Nygaard, Egil Andre & Størdal, Ketil (2025). The Macronutrient Contents of Donor Human Milk Were Not Impaired After 6 Months of Lactation. Acta Paediatrica. ISSN 0803-5253. 114(10), p. 2675–2682. doi: 10.1111/apa.70162. Full text in Research Archive Show summary

  Aim The aim of this study was to determine the energy and macronutrient contents in donor human milk longitudinally by time since delivery. Methods This prospective observational study was conducted in two Norwegian human milk banks from July 2018 to March 2022. The milk donors provided morning and evening samples of expressed milk once monthly until they stopped lactating. We used mid-infrared human milk analysers to measure the macronutrient contents. Changes by time were studied in paired t-tests and mixed regression models. Results We analysed 446 samples of milk from 34 mothers. The mean energy content was 80 at 1–6 months versus 85 kcal/100 mL at 7–12 months of lactation (p = 0.03). Corresponding figures for fat, carbohydrates and protein were 4.7 versus 5.2 g/100 mL (p = 0.03), 8.3 versus 8.1 g/100 mL (p = 0.08) and 0.86 versus 0.91 g/100 mL (p = 0.16), respectively. The protein contents initially decreased, followed by a gradual increase after 6 months. The variations within and between mothers were much larger than the observed changes by time. Conclusion The macronutrient content of donor human milk was not impaired after 6 months of lactation. Common milk bank practices of restricting milk donation to the first months of lactation appear unnecessary.

• Øymar, Maren Våland; Selvakumar, Joel Pradeepkumar; Dalen, Ingvild; Klaseie, Ken Erik; SIVANANTHAM, UJINTHINI & Øvsthus, Kasper Kavli [Show all 12 contributors for this article] (2025). Regional Differences and Time Trends in the Treatment of Infants Hospitalised With Bronchiolitis in Norway. Acta Paediatrica. ISSN 0803-5253. 115(2), p. 378–387. doi: 10.1111/apa.70338. Full text in Research Archive
• Östman, Maria Linn Olivia; Stene, Lars Christian Mørch; Tapia, German; Kivelä, Laura; Kurppa, Kalle & Størdal, Ketil (2025). Risk of Celiac Disease Before and After Nationwide Infant Rotavirus Vaccination: A Population-Based Study. Journal of Pediatrics. ISSN 0022-3476. 290. doi: 10.1016/j.jpeds.2025.114938. Full text in Research Archive Show summary

  Objective To study the association between rotavirus vaccination and risk of celiac disease, which remains debated. Study design We conducted a nationwide register-based study including 740 744 children born during 2007-2019 from the Norwegian Birth Registry individually linked to the Norwegian Patient Registry for celiac disease diagnosis. With follow-up until 5 years of age, 2795 were diagnosed with celiac disease. The main analysis was an interrupted time series analysis to assess break in trend of celiac disease incidence before compared with after vaccine introduction in September 2014. Furthermore, we linked the cohort to the Norwegian Immunization Register and compared the risk of celiac disease between fully vaccinated and nonvaccinated children. In sensitivity analyses, we excluded children born 1 year before to 1 year after vaccine introduction to mitigate the effect of herd immunity. Results There was no significant break in trend after rotavirus vaccine introduction (P = .46). Hazard ratio (HR) of celiac disease was 0.96 (95% CI 0.89-1.04) if born after compared with before vaccination started, and 1.00 (95% CI 0.92-1.09) when excluding children born in 2013-2015. In fully vaccinated compared with nonvaccinated the HR was 0.99 (95% CI 0.92-1.07), consistent in robustness analyses. Including a requirement for gluten-free diet support in the celiac disease case definition gave similar results (HR 1.06, 95% CI 0.98-1.15). Conclusions This study did not find an association between rotavirus vaccine and the risk of early-onset celiac disease.

• Greve-Isdahl, Margrethe; Møller, Thea Kristine Rogne; Bekkevold, Terese; Baranowska-Hustad, Marta Natalia; Halle, Cathinka Lønning & Laake, Ida [Show all 11 contributors for this article] (2025). Maternal and infant immunity against Bordetella pertussis, Norway, 2020 to 2023. Eurosurveillance. ISSN 1025-496X. 30(50). doi: 10.2807/1560-7917.es.2025.30.50.2500450. Full text in Research Archive Show summary

  BACKGROUND Pertussis remains a serious threat to young infants. In Norway, infants receive an acellular pertussis vaccine (aP) according to a 2 + 1 schedule at 3, 5 and 12 months of age, delivered as a hexavalent vaccine. AIM We aimed to study susceptibility to pertussis in mothers and infants to guide decisions regarding vaccination in pregnancy. METHODS In this prospective observational study, we included 366 mother/infant pairs during 2020–2023, collecting blood samples from mothers in late pregnancy, cord blood at delivery and from infants before their first and after their third vaccine dose. We retrieved health registry data on vaccination and pregnancy-related information. IgG antibody levels against pertussis-antigens, diphtheria and tetanus were measured using a multiplex immunoassay. RESULTS Of the pregnant women, 48% (174/366) had low levels of antibodies against pertussis toxin (PT) defined as below 5 IU/mL. Maternal antibodies declined in infants from birth until first vaccination, leaving 72% (154/215) of infants with anti-PT IgG levels below 5 IU/mL. All infants responded well to vaccination and we found no evidence of blunting from high levels (> 40 IU/mL) of maternal antibodies against PT. Infants of mothers who received an aP-containing booster vaccine within 2 years before pregnancy displayed low anti-PT IgG levels, with 58% (15/26) having levels below 5 IU/mL. CONCLUSION A high proportion of pregnant women and their infants under 3 months of age had low anti-PT antibody levels, indicating high susceptibility to pertussis. The results support the introduction of vaccination against pertussis during pregnancy in Norway.

• Lerchova, Tereza; Ludvigsson, Johnny; Mårild, Staffan; Imberg, Henrik; Andersson, Björn & Størdal, Ketil [Show all 7 contributors for this article] (2025). Early-Life Body Mass Index and Inflammatory Bowel Disease Risk: A Scandinavian Birth Cohort Study. Inflammatory Bowel Diseases. ISSN 1078-0998. 31(12), p. 3327–3336. doi: 10.1093/ibd/izaf167. Full text in Research Archive
• Kvenshagen, Line Norman; Solevåg, Anne Lee; Rettedal, Siren Irene; Kibsgaard-Petersen, Amalie; Eilevstjønn, Joar & Holte, Kari [Show all 7 contributors for this article] (2025). Preterm Infants Who Did Not Need Positive Pressure Ventilation Had a Lower Heart Rate Immediately After Birth Than Healthy Term Infants. Acta Paediatrica. ISSN 0803-5253. 114(8), p. 2035–2043. doi: 10.1111/apa.70079. Full text in Research Archive Show summary

  Aim Our aim was to use electrocardiograms immediately after birth to determine the heart rates of healthy newborn infants by gestational age and mode of delivery. Methods This prospective observational study was performed in two Norwegian hospitals from March 2019 to June 2021. We included infants with gestational ages of ≥ 28 weeks and no need for positive pressure ventilation. Continuous heart rate data were collected using dry electrode technology and were used to create percentile charts and compare heart rates by groups. Results We enrolled 214 preterm and 2191 term newborn infants. The median (quartiles) heart rate at 60 s of age was 166 (150–181) beats per minute for preterm infants and 174 (158–187) for term infants (p < 0.05). Term infants born using vacuum extraction, forceps or emergency Caesarean sections had significantly higher heart rates than term infants born by unassisted vaginal deliveries or planned Caesarean sections. The median heart rates of the groups were all within the normal range. Conclusion This study provided normative heart rate data for healthy newborn infants, by gestational age and delivery mode. Although the differences between the groups were statistically significant, they were of limited clinical significance and would not support changes in neonatal resuscitation measures.

• Størdal, Ketil; Christensen, Aurora; Stene, Lars Christian Mørch & Strøm, Marianne Sørlie (2025). Child and adolescent deaths by socioeconomic status in a high-income country: a cohort study. BMJ Open. 15, p. 1–10. doi: 10.1136/bmjopen-2025-099603. Full text in Research Archive Show summary

  Objective To study time trends in mortality <18 years by parental education and household income. Design Cohort study with individual-level sociodemographic variables and cause of death data. We estimated HRs for child death adjusted for sex, birth year and country background. Setting Norway, a high-income country with free access to healthcare. Participants All individuals under 18 years of age living in Norway and regardless of country of birth were included, yielding 3 015 222 individuals. Exposures Maternal and paternal education, and standardised household income. Main outcome measures Death <18 years, in four age groups and for 11 categories of causes of death. Results The child mortality rate declined from 74.7 to 19.4 per 100 000 person-years between 1990 and 2022. The adjusted HR (aHR) was 1.55 (95% CI 1.48 to 1.63) for the lowest and 1.23 (1.18 to 1.28) for the intermediate, compared with the highest level of maternal education. The aHR comparing low and high maternal education increased from 1.51 in the first to 1.60 in the second half of the observation period (p(interaction)=0.001). The aHR for low versus high maternal education was highest for age 1–11 months 2.33 (2.08 to 2.61) and weakest for 5–17 years 1.17 (1.07 to 1.27), and significantly increased across causes of death except for suicide and cancer. Paternal education yielded similar associations with mortality compared with maternal education. Household income was inversely associated with mortality, particularly for the lowest third. Conclusion We observed significant differences in mortality by parental education and income in all age categories <18 years and for most causes of death.

• Andersen, Svend; Bernklev, Tomm; Størdal, Ketil; Hagen, Milada; Kristensen, Vendel Ailin & Opheim, Randi [Show all 13 contributors for this article] (2025). Specific phenotypes may drive an increased incidence of pediatric inflammatory bowel disease in South‐Eastern Norway. Journal of Pediatric Gastroenterology and Nutrition - JPGN. ISSN 0277-2116. 81(5), p. 1227–1236. doi: 10.1002/jpn3.70148. Full text in Research Archive Show summary

  Abstract Objectives Pediatric inflammatory bowel disease (PIBD) incidence has increased in recent decades but may be stabilizing, prompting exploration of incidence changes, disease distribution, and severity. Methods From 2017 to 2019, patients under 18 years with PIBD symptoms were recruited from nine hospitals in South‐Eastern Norway for Inflammatory Bowel Disease in South‐Eastern Norway III (IBSEN III), a population‐based inception cohort study. The primary outcome was a diagnosis of any PIBD subtype as defined by revised Porto criteria. Paris classification system defined disease phenotypes, and descriptions of covariates were gathered from patients in IBSEN III. Results We identified 324 PIBD patients, with 216 consenting to the IBSEN III study. The crude incidence rate was 17.8 per 100,000 person‐years (PY) (95% confidence interval [CI]: 15.9–19.8). Crohn's disease (CD) was found in 118 patients (54.6%); 48% had ileocolonic distribution, 40% had upper gastrointestinal disease, and 12.8% had perianal disease. Complications (stricturing and/or penetrating) were noted in 18%. Ulcerative colitis (UC) was diagnosed in 78 patients (36.1%), predominantly pancolitis (41%), with 30% having proctitis. One in five suffered severe disease. IBD unclassified was found in 20 patients (9.3%). PIBD incidence in those under 16 was 13.6/100,000 PY, up from 4.7 in the IBSEN study 27 years ago. Terminal ileitis (11%–23%) and proctitis (14%–25%) rose from IBSEN (1990–1993) to IBSEN III, while stricturing/penetrating disease changed insignificantly (17%–16%). Conclusions The incidence of PIBD has risen in South‐Eastern Norway, with increased cases of terminal ileitis in CD, unchanged stricturing/penetrating disease, and increased proctitis in UC compared to the original IBSEN study. Trial registration ClinicalTrials.gov identifier: NCT02727959.

• Thomassen, Rut Anne; Kvammen, Janne Anita; Bentsen, Beint Sigmund; Bratlie, Marianne; Bøhn, Siv Kjølsrud & Farstad, Hanne [Show all 15 contributors for this article] (2025). Effect of prebiotics on gastrointestinal symptoms and quality of life in children with intestinal failure: A pilot study. Journal of Pediatric Gastroenterology and Nutrition - JPGN. ISSN 0277-2116. 81(4), p. 975–985. doi: 10.1002/jpn3.70186. Full text in Research Archive Show summary

  Objectives Children with intestinal failure (IF) have a substantial disease burden, with significant gastrointestinal (GI) symptoms, abnormal stool patterns and reduced health-related quality of life (HRQOL). This study examined the effects of prebiotic supplementation on GI symptoms and HRQOL. Methods An open-label, randomised controlled trial involving two phases. In Phase 1, children aged 1–18 years with IF received supplementation with a blend of prebiotics for 4 weeks. In Phase 2, participants were randomised to either continue supplementation or cease supplementation for 6 months to evaluate long-term effects. Primary end points included parent-reported GI symptoms and HRQOL, measured by PedsQL™ scales. Secondary end points were stool consistency and frequency, nutritional support and antibiotic use. Results Out of 47 children completing Phase 1, 43 completed Phase 2 (24 in the intervention group, 19 in the control group). After 4 weeks, 60% reported reduced GI symptoms. By the end of Phase 2, the intervention group showed no significant changes in HRQOL score, but significant GI symptom improvements compared to controls (mean paediatric quality of life inventory GI score difference of 6.9, p = 0.01). Stool frequency decreased (median −1.0 vs. 0 stools/day, p = 0.003), and stool consistency normalised more frequently in the intervention group (42% vs. 6%, p = 0.02). No significant changes were noted in nutritional support or antibiotic use. Conclusion While HRQOL remained unchanged, short- and long-term prebiotic supplementation significantly improved GI symptoms, stool frequency and stool consistency in children with IF, indicating its potential as a therapeutic option in paediatric IF.

• Segerstad, Elin Malmberg Hård af; Guo, Annie; Mårild, Karl Staffan; Stene, Lars Christian Mørch; Brantsæter, Anne Lise & Størdal, Ketil (2025). Associations of early life dietary diversity and healthy eating with celiac disease: A prospective cohort study. Clinical Nutrition. ISSN 0261-5614. 52, p. 171–178. doi: 10.1016/j.clnu.2025.07.012. Full text in Research Archive
• Størdal, Ketil & Beck, Carolyn E. (2025). Reducing the use of proton pump inhibitors in infants with gastroesophageal reflux symptoms. Canadian Family Physician (CFP). ISSN 0008-350X. 71(3), p. 170–172. doi: 10.46747/cfp.7103170. Full text in Research Archive Show summary

  Regurgitation, often referred to as gastroesophageal reflux, is a physiological phenomenon. Most infants younger than 1 year of age regurgitate 2 or more times daily in the first months of life; this normal behaviour should be differentiated from gastroesophageal reflux disease (GERD) or other worrisome diagnoses. There should be a suspicion of GERD when infants fail to grow due to feeding difficulties. Infants’ refluxate is less acidic due to lower gastric acid output and the buffering effects of frequent milk feeds, which differs from older age groups. Despite many randomized trials, proton pump inhibitors (PPIs) have not proven to reduce the symptoms of suspected reflux disease in infants. Therefore, infants should not be prescribed PPIs unless careful investigation by specialists concludes a diagnosis of GERD.

• Dåstøl, Vilde Øverlien; Haftorn, Kristine Løkås; Rudsari, Hamid Khoshfekr; Jaholkowski, Piotr Pawel; Størdal, Ketil & Håberg, Siri Eldevik [Show all 12 contributors for this article] (2025). Maternal seafood intake, dietary contaminant exposure, and risk of juvenile idiopathic arthritis: exploring gene-environment interactions. Frontiers in Immunology. 15. doi: 10.3389/fimmu.2024.1523990. Full text in Research Archive Show summary

  Objectives: Juvenile idiopathic arthritis (JIA) originates from a complex interplay between genetic and environmental factors. We investigated the association between seafood intake and dietary contaminant exposure during pregnancy and JIA risk, to identify sex differences and gene-environment interactions. Methods: We used the Norwegian Mother, Father, and Child Cohort Study (MoBa), a population-based prospective pregnancy cohort (1999–2008). JIA patients were identified through the Norwegian Patient Registry, with remaining mother-child pairs serving as controls. We assessed maternal seafood intake and dietary contaminants typically found in seafood using a food frequency questionnaire completed during pregnancy, mainly comparing high (≥90th percentile, P90) vs low (<P90) intake. Multivariable logistic regression calculated adjusted odds ratios (aOR), including sex-stratification analyses. A polygenic risk score (PRS) for JIA was used in a subsample to assess gene-environment interactions. Results: We identified 217 JIA patients and 71,884 controls. High vs low maternal intake of lean/semi-oily fish was associated with JIA (aOR 1.51, 95% CI 1.02-2.22), especially among boys (aOR 2.13, 95% CI 1.21-3.75). A significant gene-environment interaction was observed between total fish intake and PRS, with high fish intake associated with JIA primarily in those with low PRS (p<0.03). We found no associations between high vs low exposure to other types of seafood or environmental contaminants and JIA. Conclusions: We found a modestly increased risk of JIA associated with high intake of lean/semi-oily fish during pregnancy, not explained by estimated exposure to dietary contaminants. Our data suggest a more pronounced association in children with a lower genetic predisposition for JIA.

• Solvang, Thale Amalie Westre; Bråten, Vilde; Størdal, Ketil; Tveiten, Lars; Lang, Astri Maria & Eriksen, Beate Horsberg [Show all 8 contributors for this article] (2025). Admission temperature in very preterm infants 2012–2021: a Nationwide Quality Registry Study, Norway. BMJ Paediatrics Open. 9(1), p. 1–10. doi: 10.1136/bmjpo-2024-003263. Full text in Research Archive Show summary

  Objective To examine the distribution and time trends of admission temperature in very preterm infants, effects of temperature-preserving interventions and associations between hypothermia and outcomes. Methods Population-based cohort study of infants <32 gestational weeks without lethal malformations admitted to a neonatal intensive care unit within 2 hours of birth between 1 January 2012 and 31 December 2021. Hypothermia was defined as mild (36.0°C–36.4°C), moderate (34.5°C–35.9°C) or severe (<34.5°C). Associations between admission temperature and outcomes were investigated using multivariate logistic regression, adjusting for sex, weight Z-score, gestational age, antenatal steroids, surfactant and hospital. Results In total, 2457/4879 (50.4%) had normal admission temperatures between 36.5°C and 37.5℃, 1314 (26.9%) had mild hypothermia and 886 (18.2%) had moderate to severe hypothermia, with a significant interhospital variance of 7%–40%. Moderate to severe hypothermia decreased from 24% in 2012 to 16% in 2021 (ptrend<0.001). Measuring temperature before leaving the delivery unit correlated with lower incidence of moderate to severe hypothermia (42% vs 58%, p<0.001). Admission temperature was inversely associated with mortality (adjusted OR 1.5, 95% CI 1.1 to 2.0 for moderate and 2.4, 95% CI 1.1 to 4.9 for severe hypothermia) and with surgical necrotising enterocolitis or intestinal perforation (adjusted OR 1.7, 95% CI 1.1 to 2.7 for moderate and 3.1, 95% CI 1.3 to 7.7 for severe hypothermia). Conclusions Although the incidence of hypothermia decreased during the study period, it remains a concern due to significant associations with adverse outcomes. Areas for further improvement include addressing interhospital variance and enhancing temperature monitoring in the delivery unit.

• Størdal, Ketil & Kurppa, Kalle (2025). Celiac disease, non-celiac wheat sensitivity, wheat allergy – clinical and diagnostic aspects. Seminars in Immunology. ISSN 1044-5323. 77, p. 1–7. doi: 10.1016/j.smim.2025.101930. Full text in Research Archive
• Guo, Annie; Ludvigsson, Johnny; Lerchova, Tereza; Imberg, Henrik; Størdal, Ketil & Mårild, Karl Staffan (2024). Association between Maternal Infections in Pregnancy and the Risk of Inflammatory Bowel Disease in the Offspring: Findings from Two Scandinavian Birth Cohorts. Inflammatory Bowel Diseases. ISSN 1078-0998. 31(7), p. 1761–1771. doi: 10.1093/ibd/izae209. Full text in Research Archive Show summary

  Background The association of infections and antibiotic use in pregnancy and the risk of inflammatory bowel disease (IBD) development in the offspring have been scarcely investigated. We examined infection and antibiotic use in pregnancy and the risk of IBD in offspring. Methods We followed participants from the All Babies in Southeast Sweden (ABIS) and the Norwegian mother father and child cohort (MoBa) from birth (1997-2009) until 2020-2021. IBD diagnosis was classified as ≥2 records in national registers. Information on infections (any, gastrointestinal, and respiratory), their timing (early or late in pregnancy), and antibiotic use in pregnancy were collected from questionnaires. Cox proportional-hazard regression and meta-analytic methods were used to estimate pooled adjusted hazard ratios (aHRs) for IBD and its subtypes, adjusted for parental IBD, maternal smoking, and education. Sensitivity analyses accounted for exposure to antibiotics and infections 0-12 months of age. Results We followed 117 493 children for 2 024 299 person-years (follow-up 22.3 years in ABIS and 16.4 years in MoBa), including 451 IBD cases. The aHRs for any infection and respiratory infections in pregnancy and offspring IBD were close to one (aHR = 0.99 [95% CI = 0.73-1.33] and aHR = 1.00 [95% CI = 0.81-1.23], respectively). However, any versus no infection in early pregnancy was associated with IBD development (aHR = 1.26 [95% CI = 1.02-1.55]), particularly Crohn’s disease (CD; aHR = 1.40 [95% CI = 1.01-1.93]). Any versus no gastrointestinal infection in late pregnancy was associated with offspring CD (aHR = 1.95 [95% CI = 1.34-2.84]). Antibiotic use in pregnancy was not associated with IBD in the child (aHR = 1.15 [95% CI = 0.93-1.44]). Conclusions In this binational birth cohort study, the risk of offspring IBD varied by infection type and timing but not with maternal antibiotic use in pregnancy.

• Bøås, Håkon; Storm, Margrethe Larsdatter; Tapia, German; Kristoffersen, Anja Bråthen; Løvlie, Astrid Louise & Størdal, Ketil [Show all 10 contributors for this article] (2024). Frequency and risk of SARS-CoV-2 reinfections in Norway: a nation-wide study, February 2020 to January 2022. BMC Public Health. 24(1). doi: 10.1186/s12889-024-17695-8. Full text in Research Archive Show summary

  Background SARS-CoV-2 reinfection rates have been shown to vary depending on the circulating variant, vaccination status and background immunity, as well as the time interval used to identify reinfections. This study describes the frequency of SARS-CoV-2 reinfections in Norway using different time intervals and assesses potential factors that could impact the risk of reinfections during the different variant waves. Methods We used linked individual-level data from national registries to conduct a retrospective cohort study including all cases with a positive test for SARS-CoV-2 from February 2020 to January 2022. Time intervals of 30, 60, 90 or 180 days between positive tests were used to define potential reinfections. A multivariable Cox regression model was used to assess the risk of reinfection in terms of variants adjusting for vaccination status, demographic factors, and underlying comorbidities. Results The reinfection rate varied between 0.2%, 0.6% and 5.9% during the Alpha, Delta and early Omicron waves, respectively. In the multivariable model, younger age groups were associated with a higher risk of reinfection compared to older age groups, whereas vaccination was associated with protection against reinfection. Moreover, the risk of reinfection followed a pattern similar to risk of first infection. Individuals infected early in the pandemic had higher risk of reinfection than individuals infected in more recent waves. Conclusions Reinfections increased markedly during the Omicron wave. Younger individuals, and primary infections during earlier waves were associated with an increased reinfection risk compared to primary infections during more recent waves, whereas vaccination was a protective factor. Our results highlight the importance of age and post infection waning immunity and are relevant when evaluating vaccination polices.

• Segerstad, Elin Malmberg Hård af; Borge, Tiril Cecilie; Guo, Annie; Mårild, Karl Staffan; Stene, Lars Christian Mørch & Brantsæter, Anne Lise [Show all 7 contributors for this article] (2024). Associations of Pregnancy Dietary Quality and Diversity with Childhood Celiac Disease. Journal of Nutrition. ISSN 0022-3166. 154(12), p. 3770–3779. doi: 10.1016/j.tjnut.2024.10.033. Full text in Research Archive Show summary

  Background High gluten and low dietary fiber in pregnancy intake is associated with an increased risk of celiac disease (CeD) in the child. Early life higher dietary quality is suggested to reduce the subsequent risk of CeD. Objectives The aim was to investigate associations of pregnancy dietary quality and diversity with child risk of CeD. Methods In The Norwegian Mother, Father and Child Cohort Study, 85,122 mother-child pairs had available data from a validated pregnancy food frequency questionnaire. Pregnancy dietary quality and diversity were estimated by a Pregnancy Healthy Eating Index [mean 99.3, standard deviation (SD) 9.9, range 48.8–128.3], and a Diet Diversity Score (mean 7.0, SD 1.0, range 1.6–9.8), respectively. Child CeD was captured by ≥2 diagnostic codes in the Norwegian Patient Registry. Logistic regression was used to estimate associations between pregnancy dietary quality, diversity and child CeD, adjusted for socioeconomic factors, and parents CeD [adjusted odds ratio (aOR), 95% confidence intervals (CI)]. CeD-susceptible human leukocyte antigen haplotypes (DQ2/DQ8) were present in 30,718 (45.5%). Results Up to mean age 16.0 (SD 1.8, 12.4–19.8) y, 1363 (1.6%) children were diagnosed with CeD. Lower as well as higher pregnancy dietary quality associated with a reduced risk of CeD in the child (<5th percentile aOR = 0.67, 95% CI: 0.48, 0.93, >95th percentile aOR = 0.71, 95% CI: 0.52, 0.98, respectively, nonlinear squared term P = 0.011). Analyses on genetically susceptible children, adjustments for pregnancy iron supplementation, gluten, and dietary fiber intake, and child early life dietary quality, gluten intake and iron supplementation, supported the finding. Pregnancy dietary diversity was not associated with child CeD (aOR = 1.00, 95% CI: 0.94, 1.07/score). Conclusions In this population-based study, lower as well as higher pregnancy dietary quality associated with a reduced risk of CeD diagnosis in the child. In contrast, no such association was observed with maternal dietary diversity.

• Dimopoulou, Varvara; Klingenberg, Claus Andreas; Navér, Lars; Nordberg, Viveka; Berardi, Alberto & Helou, Salhab el [Show all 46 contributors for this article] (2024). Antibiotic exposure for culture-negative early-onset sepsis in late-preterm and term newborns: an international study. Pediatric Research. ISSN 0031-3998. doi: 10.1038/s41390-024-03532-6. Full text in Research Archive Show summary

  Background - Early-life antibiotic exposure is disproportionately high compared to the burden of culture-proven early-onset sepsis (CP-EOS). We assessed the contribution of culture-negative cases to the overall antibiotic exposure in the first postnatal week.<p> <p>Methods - We conducted a retrospective analysis across eleven countries in Europe, North America, and Australia. All late-preterm and term infants born between 2014 and 2018 who received intravenous antibiotics during the first postnatal week were classified as culture-negative cases treated for ≥5 days (CN ≥ 5d), culture-negative cases treated for <5 days (CN < 5d), or CP-EOS cases.<p> <p>Results - Out of 757,979 infants, 21,703 (2.9%) received intravenous antibiotics. The number of infants classified as CN ≥ 5d, CN < 5d, and CP-EOS was 7996 (37%), 13,330 (61%), and 375 (1.7%). The incidence of CN ≥ 5d, CN < 5d, and CP-EOS was 10.6 (95% CI 10.3–10.8), 17.6 (95% CI 17.3–17.9), and 0.49 (95% CI 0.44–0.54) cases per 1000 livebirths. The median (IQR) number of antibiotic days administered for CN ≥ 5d, CN < 5d, and CP-EOS was 77 (77–78), 53 (52–53), and 5 (5-5) per 1000 livebirths.<p> <p>Conclusions - CN ≥ 5d substantially contributed to the overall antibiotic exposure, and was 21-fold more frequent than CP-EOS. Antimicrobial stewardship programs should focus on shortening antibiotic treatment for culture-negative cases.

• Hestetun, Sigrid Valen; Rudsari, Hamid Khoshfekr; Jaholkowski, Piotr Pawel; Shadrin, Alexey; Haftorn, Kristine Løkås & Andersen, Svend [Show all 13 contributors for this article] (2024). Incidence and Genetic Risk of Juvenile Idiopathic Arthritis in Norway by Latitude. Arthritis & Rheumatology. ISSN 2326-5191. 77(4), p. 458–467. doi: 10.1002/art.43040. Full text in Research Archive Show summary

  Objective: We aimed to investigate the incidence of juvenile idiopathic arthritis (JIA) in the three geographic regions of Norway and whether potential regional incidence differences are explained by environmental or genetic factors across regions. Methods: We conducted a register-based cohort study including all Norwegian children born from 2004 to 2019, with follow-up throughout 2020. The JIA diagnosis, defined by at least two International Classification of Diseases, Tenth Revision codes for JIA, was validated against medical records. The incidence rate (IR) and hazard ratio (HR) for JIA were estimated for all Norway and for the North, Mid, and South regions. In a subsample from the Norwegian Mother, Father, and Child Cohort Study (MoBa), the genetic risk for JIA was assessed in the three regions. Results: After median 9.1 (range 0.3-16.0) years of follow-up, we identified 1,184 patients with JIA and 910,058 controls. The IR for JIA/100,000 person-years was 14.4 in all of Norway, 25.9 in the North region, 17.9 in the Mid region, and 12.5 in the South region. The HR (95% confidence interval [CI]) of JIA in the North region was 2.07 (1.77-2.43) and in the Mid region HR 1.43 (95% CI 1.23-1.67) compared with the South region. Adjustments for perinatal factors, socioeconomic status, and early antibiotic exposure did not change our estimates substantially. In MoBa (238 patients with JIA, 57,392 controls), the association between JIA and region of birth was no longer significant when adjusting for genetic factors. Conclusion: We found a higher incidence of JIA with increasing latitude without evidence for available environmental factors explaining the observed gradient. In contrast, genetic factors modified the association, but further studies are warranted.

• Jankauskaite, Lina; Wyder, Corinne; Torso, Stefano del; Mamenko, Marina; Trapani, Sandra & Grossman, Zachi [Show all 15 contributors for this article] (2024). Over-investigation and overtreatment in pediatrics: a survey from the European Academy of Paediatrics and Japan Pediatric Society. Frontiers in Pediatrics. 12. doi: 10.3389/fped.2024.1333239. Full text in Research Archive Show summary

  Introduction: Avoiding over-investigation and overtreatment in health care is a challenge for clinicians across the world, prompting the international Choosing Wisely campaign. Lists of recommendations regarding medical overactivity are helpful tools to guide clinicians and quality improvement initiatives. We aimed to identify the most frequent and important clinical challenges related to pediatric medical overactivity in Europe and Japan. Based on the results, we aim to establish a (European) list of Choosing Wisely recommendations. Methods: In an online survey, clinicians responsible for child health care in Europe and Japan were invited to rate 18 predefined examples of medical overactivity. This list was compiled by a specific strategic advisory group belonging to the European Academy of Paediatrics (EAP). Participants were asked to rate on a Likert scale (5 as the most frequent/important) according to how frequent these examples were in their working environment, and how important they were considered for change in practice. Results: Of 2,716 physicians who completed the survey, 93% (n = 2,524) came from 17 countries, Japan (n = 549) being the largest contributor. Pediatricians or pediatric residents comprised 89%, and 51% had 10–30 years of clinical experience. Cough and cold medicines, and inhaled drugs in bronchiolitis were ranked as the most frequent (3.18 and 3.07 on the Likert scale, respectively), followed by intravenous antibiotics for a predefined duration (3.01), antibiotics in uncomplicated acute otitis media (2.96) and in well-appearing newborns. Regarding importance, the above-mentioned five topics in addition to two other examples of antibiotic overtreatment were among the top 10. Also, IgE tests for food allergies without relevant medical history and acid blockers for infant GER were ranked high. Conclusion: Overtreatment with antibiotics together with cough/cold medicines and inhaled drugs in bronchiolitis were rated as the most frequent and important examples of overtreatment across countries in Europe and Japan.

• Sahli, Sarah & Størdal, Ketil (2024). Systematic review of socioeconomic factors and COVID-19 in children and adolescents. Acta Paediatrica. ISSN 0803-5253. 113, p. 384–393. doi: 10.1111/apa.17091. Full text in Research Archive Show summary

  Aim To systematically review the evidence on Covid-19 infection risk, severity and vaccination uptake among children and adolescents by socioeconomic status. Methods We conducted a systematic literature review, using the PubMed database. We searched for articles published from January 2020 to January 2022 using “MeSH” words and titles. The key terms were “COVID”, “social status”, “socioeconomic factor” and “children”. We also searched secondary sources such as published reports and other databases. Results The search identified 14 relevant articles and reports. This review shows that children of lower socioeconomic status have a higher risk of COVID-19 infection and a higher risk of being hospitalised. Mortality in a global setting was also higher in children with low socioeconomic status, though not observed in high-resourced countries. These children are also less likely to be vaccinated against the SARS-CoV-2 virus. Conclusions The higher risk of COVID-19 infection and hospitalisation and lower vaccination coverage in children and adolescents from lower socioeconomic backgrounds demonstrate health disparities also in young age. These disparities should inform health authorities in planning for future pandemics.

• Guo, Annie; Ludvigsson, Johnny; Segerstad, Elin Malmberg Hård af; Brantsæter, Anne Lise; Andersson, Björn & Størdal, Ketil [Show all 7 contributors for this article] (2024). Early-Life Diet Diversity and the Subsequent Risk of Inflammatory Bowel Disease: Findings From Two Scandinavian Birth Cohorts. Inflammatory Bowel Diseases. ISSN 1078-0998. 31(6), p. 1493–1501. doi: 10.1093/ibd/izae210. Full text in Research Archive Show summary

  Background Diet diversity in early childhood promotes microbial diversity, influences the developing immune system, and has been linked to a reduced risk of immune-mediated diseases. This study aimed to determine the association between childhood diet diversity and later inflammatory bowel disease (IBD), for which data are limited. Methods Questionnaire data from the population-based birth cohorts All Babies in Southeast Sweden (ABIS) and the Norwegian Mother, Father, and Child Cohort (MoBa), including participants from Southeast Sweden and Norway, were used to estimate a diet diversity score at ages 1 and 3 years. This score represents the diversity of intakes across 5 food groups comprising 11 subgroups. A higher score signifies higher diet diversity. We used linked health registry data to identify IBD diagnoses up to the year 2021. Cox regression and random-effect models were used to estimate pooled hazard ratios (aHRs) adjusted for sociodemographics, breastfeeding, and early-life antibiotic use. Results Among 81 272 children with 1 304 325 person-years of follow-up, 307 developed IBD. Diet diversity at ages 1 and 3 years was in pooled analyses not associated with later IBD (per one-unit increase, aHR = 0.96 [95% CI = 0.81-1.14] and aHR = 0.96 [95% CI = 0.83-1.11]). In MoBa, but not ABIS, a higher diet diversity at 1 and 3 years of age was inversely associated with ulcerative colitis (UC) (per one-unit increase, aHR = 0.78 [95% CI = 0.66-0.94] and aHR = 0.78 [95% CI = 0.65-0.95]). Still, pooled aHRs for UC as well as Crohn’s disease approximated one. Conclusions In this prospective study of 2 Scandinavian birth cohorts, no association was observed between early-life diet diversity and the subsequent risk of IBD.

• Agrawal, Manasi; Størdal, Ketil; Hansen, Anne Vinkel; Östensson, Malin; Freitas, Maiara Brusco De & Allin, Kristine H. [Show all 9 contributors for this article] (2024). Breastfeeding Duration Is Not Associated With Offspring Inflammatory Bowel Disease Risk in Three Population-Based Birth Cohorts. Clinical Gastroenterology and Hepatology. ISSN 1542-3565. 22(12), p. 2459–2467. doi: 10.1016/j.cgh.2024.04.013. Full text in Research Archive Show summary

  Background & Aims Breastfeeding is critical for offspring health and development. Although many observational studies report a protective effect between breastfeeding and inflammatory bowel disease (IBD), the relationship is not well-understood. Methods We used prospectively collected data from 3 population-based birth cohorts (Danish National Birth Cohort, Norwegian Mother, Father, and Child Cohort, and All Babies in Southeast Sweden) and cross-linked national registers to ascertain the impact of breastfeeding duration on offspring IBD risk in each country, using adjusted Cox proportional regression analyses. We performed meta-analyses to determine pooled estimates. Results We included 148,737 offspring and 169,510 offspring in analyses of exclusive and any breastfeeding duration, respectively. During median follow-up of 16.3–22.3 years, between 1996 and 2021, 543 offspring were diagnosed with IBD. In each country, there was no association between exclusive breastfeeding duration and offspring IBD risk after adjusting for birth year (Denmark), offspring sex, parental IBD status, maternal education, smoking during pregnancy, age at delivery, mode of delivery, preterm birth, and small for gestational age. The pooled adjusted hazard ratio for IBD was 1.24 (95% confidence interval, 0.94–1.62; Q = 0.16, I2 = 0.0%) and 1.02 (95% confidence interval, 0.85–1.21; Q = 1.45, I 2= 0.0%) among offspring breastfed exclusively for ≥6 months and <4 months, respectively, compared with 4–5 months. Similarly, we found null associations in pooled analyses of any breastfeeding duration and IBD, subtypes Crohn’s disease and ulcerative colitis, as well as in cohort-specific analyses. Conclusions In prospectively collected data from 3 population-based birth cohorts, the duration of exclusive or any breastfeeding was not associated with offspring IBD risk.

• Guo, Annie; Brantsæter, Anne Lise; Borge, Tiril Cecilie; Segerstad, Elin Malmberg Hård af; Imberg, Henrik & Mårild, Karl [Show all 7 contributors for this article] (2024). Maternal diet in pregnancy and the risk of inflammatory bowel disease in the offspring: a prospective cohort study. American Journal of Clinical Nutrition. ISSN 0002-9165. 121(1), p. 32–39. doi: 10.1016/j.ajcnut.2024.10.017. Full text in Research Archive Show summary

  Background Diet has been hypothesized as a risk factor for the development of inflammatory bowel disease (IBD). Objective The objective of this study was to explore associations between maternal diet diversity and quality in pregnancy and the offspring’s risk of IBD. Methods We used data from a nationwide cohort study on 85,129 Norwegian children followed from birth (1999–2009) with information on maternal diet in pregnancy from validated food frequency questionnaires. Hazard ratios (HRs) for IBD, Crohn disease (CD), and ulcerative colitis (UC) by maternal diet diversity, quality, and intake amounts of individual food groups were adjusted for maternal BMI, parental IBD, and sociodemographic factors. Sensitivity analyses were adjusted for the child’s early-life diet quality and antibiotic treatment. Dietary exposures were classified into tertiles, comparing low (reference) with medium, and high levels. Results During a mean follow-up time of 16.1 y (1,367,837 person-years of follow-up), 268 children developed IBD (CD, n = 119; UC, n = 76; IBD-unclassified, n = 73). High compared with low diet diversity in pregnancy was associated with a lower risk of UC in the offspring [adjusted HR (aHR) 0.46, 95% confidence interval: 0.25, 0.87], with consistent findings after further adjustment for the child’s early-life diet quality and antibiotic treatment. High compared with low diet diversity in pregnancy yielded aHRs of 0.81 for CD (0.51–1.28) and 0.75 for any IBD (0.55–1.02) in the offspring. A high compared with low diet quality in pregnancy or intakes of specific food groups were not associated with the offspring’s risk of IBD or its subtypes. Conclusions Our findings suggest that a higher maternal diet diversity in pregnancy may be associated with a lower risk of UC in the offspring.

• Szajewska, Hania; Shamir, Raanan; Auricchio, Renata; Chmielewska, Anna; Dolinsek, Jernej & Kivelä, Laura [Show all 16 contributors for this article] (2024). Early diet and the risk of coeliac disease. An update 2024 position paper by the ESPGHAN special interest group on coeliac disease. Journal of Pediatric Gastroenterology and Nutrition - JPGN. ISSN 0277-2116. 79(2), p. 438–445. doi: 10.1002/jpn3.12280. Full text in Research Archive
• Guo, Annie; Ludvigsson, Johnny; Brantsæter, Anne Lise; Klingberg, Sofia; Östensson, Malin & Størdal, Ketil [Show all 7 contributors for this article] (2024). Early-life diet and risk of inflammatory bowel disease: A pooled study in two Scandinavian birth cohorts. Gut. ISSN 0017-5749. 73(4), p. 590–600. doi: 10.1136/gutjnl-2023-330971. Full text in Research Archive Show summary

  Objective We assessed whether early-life diet quality and food intake frequencies were associated with subsequent IBD. Design Prospectively recorded 1-year and 3-year questionnaires in children from the All Babies in Southeast Sweden and The Norwegian Mother, Father and Child Cohort Study were used to assess diet quality using a Healthy Eating Index and intake frequency of food groups. IBD was defined as >2 diagnoses in national patient registers. Cox regression yielded HRs adjusted (aHRs) for child’s sex, parental IBD, origin, education level and maternal comorbidities. Cohort-specific results were pooled using a random-effects model. Results During 1 304 433 person-years of follow-up, we followed 81 280 participants from birth through childhood and adolescence, whereof 307 were diagnosed with IBD. Compared with low diet quality, medium and high diet quality at 1 year of age were associated with a reduced risk of IBD (pooled aHR 0.75 (95% CI=0.58 to 0.98) and 0.75 (95% CI=0.56 to 1.00)). The pooled aHR per increase of category was 0.86 (0.74 to 0.99). Pooled aHR for children 1 year old with high versus low fish intake was 0.70 (95% CI=0.49 to 1.00) for IBD, and showed association with reduced risk of UC (pooled aHR=0.46; 95% CI=0.21, 0.99). Higher vegetable intake at 1 year was associated with a risk reduction in IBD. Intake of sugar-sweetened beverages was associated with an increased risk of IBD. Diet quality at 3 years was not associated with IBD. Conclusion In this Scandinavian birth cohort, high diet quality and fish intake in early life were associated with a reduced risk of IBD.

• Lund-Blix, Nicolai Andre; Bjerregaard, Anne A.; Tapia, German; Størdal, Ketil; Brantsæter, Anne Lise & Strøm, Marin [Show all 14 contributors for this article] (2024). No association between long-chain n-3 fatty acid intake during pregnancy and risk of type 1 diabetes in offspring in two large Scandinavian pregnancy cohorts. Diabetologia. ISSN 0012-186X. 67, p. 1023–1028. doi: 10.1007/s00125-024-06125-4. Full text in Research Archive Show summary

  Abstract Aims/hypothesis The aim of this study was to investigate whether higher dietary intake of marine n-3 fatty acids during pregnancy is associated with a lower risk of type 1 diabetes in children. Methods The Danish National Birth Cohort (DNBC) and the Norwegian Mother, Father and Child Cohort Study (MoBa) together include 153,843 mother–child pairs with prospectively collected data on eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake during pregnancy from validated food frequency questionnaires. Type 1 diabetes diagnosis in children (n=634) was ascertained from national diabetes registries. Results There was no association between the sum of EPA and DHA intake during pregnancy and risk of type 1 diabetes in offspring (pooled HR per g/day of intake: 1.00, 95% CI 0.88, 1.14), with consistent results for both the MoBa and the DNBC. Robustness analyses gave very similar results. Conclusions/interpretation Initiation of a trial of EPA and DHA during pregnancy to prevent type 1 diabetes in of

• Størdal, Ketil; Ma, Amy & Beck, Carolyn E. (2024). Reducing the use of proton pump inhibitors in infants with reflux symptoms. The BMJ. 385. doi: 10.1136/bmj-2022-074588. Full text in Research Archive
• Juma, Damas; Størdal, Ketil; Kamala, Benjamin; Bishanga, Dunstan R.; Kalolo, Albino & Moshiro, Robert [Show all 8 contributors for this article] (2024). Readiness to provide comprehensive emergency obstetric and neonatal care: a cross-sectional study in 30 health facilities in Tanzania. BMC Health Services Research. 24(870). doi: 10.1186/s12913-024-11317-0. Full text in Research Archive Show summary

  Background Despite the global progress in bringing health services closer to the population, mothers and their newborns still receive substandard care leading to morbidity and mortality. Health facilities’ capacity to deliver the service is a prerequisite for quality health care. This study aimed to assess health facilities’ readiness to provide comprehensive emergency obstetric and newborn care (CEmONC), comprising of blood transfusion, caesarean section and basic services, and hence to inform improvement in the quality of care interventions in Tanzania. Methods A cross-sectional assessment of 30 CEmONC health facilities implementing the Safer Births Bundle of Care package in five regions of Tanzania was carried out between December 2020 and January 2021. We adapted the World Health Organization’s Service Availability and Readiness Assessment tool to assess amenities, equipment, trained staff, guidelines, medicines, and diagnostic facilities. Composite readiness scores were calculated for each category and results were compared at the health facility level. For categorical variables, we tested for differences by Fisher’s exact test; for readiness scores, differences were tested by a linear mixed model analysis, taking into account dependencies within the regions. We used p < 0.05 as our level of significance. Results The overall readiness to provide CEmONC was 69.0% and significantly higher for regional hospitals followed by district hospitals. Average readiness was 78.9% for basic amenities, 76.7% for medical equipment, 76.0% for diagnosis and treatment commodities, 63.6% for staffing and 50.0% for guidelines. There was a variation in the availability of items at the individual health facility level and across levels of facilities. We found a significant difference in the availability of basic amenities, equipment, staffing, and guidelines between regional, and district hospitals and health centres (p = 0.05). Regional hospitals had significantly higher scores of medical equipment than district hospitals and health centers (p = 0.02). There was no significant difference in the availability of commodities for diagnosis and treatment between different facility levels. Conclusion Facilities’ readiness was inadequate and varied across different levels of the facility. There is room to improve the facilities’ readiness to deliver quality maternal and newborn care. The responsible authorities should take immediate actions to address the observed deficiencies while carefully choosing the most effective and feasible interventions and monitoring progress in readiness.

• Sigvardsson, Ida; Ludvigsson, Johnny; Andersson, Björn; Størdal, Ketil & Mårild, Karl (2024). Tobacco Smoke Exposure in Early Childhood and Later Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study. Journal of Crohn's and Colitis. ISSN 1873-9946. 18(5), p. 661–670. doi: 10.1093/ecco-jcc/jjae020. Full text in Research Archive Show summary

  Objectives To examine the association between early-life smoking exposure and later risk of inflammatory bowel disease [IBD]. Methods We followed 115663 participants from the Norwegian Mother, Father and Child [MoBa] and All Babies in Southeast Sweden [ABIS] cohorts from birth [1997–2009] through 2021. IBD was identified through national patient registers. Validated questionnaire data defined maternal smoking during pregnancy, maternal environmental tobacco smoke [ETS] exposure during pregnancy, and child ETS exposure by ages 12 and 36 months. Cox regression was used to estimate adjusted hazard ratios [aHRs] for sex, maternal age, education level, parental IBD, and origin. Cohort-specific estimates were pooled using a random-effects model. Results During 1 987 430 person-years of follow-up, 444 participants developed IBD [ABIS, 112; MoBa, 332]. Any vs no maternal smoking during pregnancy yielded a pooled aHR of 1.30 [95% CI = 0.97–1.74] for offspring IBD. Higher level of maternal smoking during pregnancy (compared with no smoking, average ≥6 cigarettes/day: pooled aHR = 1.60 [95% CI = 1.08–2.38]) was associated with offspring IBD, whereas a lower smoking level was not (average 1–5 cigarettes/day: pooled aHR = 1.09 [95% CI = 0.73–1.64]). Child ETS exposure in the first year of life was associated with later IBD (any vs no ETS, pooled aHR = 1.32 [95% CI = 1.03–1.69]). Estimates observed for child ETS exposure by 36 months were similar but not statistically significant. Conclusions In this prospective Scandinavian cohort study, children exposed to higher levels of maternal smoking during pregnancy or ETS during the first year of life were at increased risk of later IBD.

• Braa, Hanne Gaup; Mathisen, Elisabeth; Moshiro, Robert; Daudi, Vickfarajaeli X.; Francis, Fortunata & Mduma, Esto [Show all 8 contributors for this article] (2024). Hypothermia—Prevalence and risk factors in neonates admitted to a neonatal unit in Tanzania. Acta Paediatrica. ISSN 0803-5253. p. 1–9. doi: 10.1111/apa.17499. Full text in Research Archive Show summary

  Aim We aimed to study the prevalence of hypothermia among neonates, the association between admission temperature and neonatal mortality, and the impact of radiant warmers. Methods In an observational prospective study, we included 1988 neonates born at Haydom Lutheran Hospital, Tanzania, and admitted to the neonatal unit from 1 January 2018 to 31 December 2022. We explored risk factors for hypothermia (<36.0°C, primary outcome) and newborn mortality by admission temperature (secondary outcome) with adjusted odds ratios (aOR) and 95% confidence intervals (CI) for birth weight and bag and mask ventilation. Results Hypothermia was present in 47.0% (n = 935) at admission, 46.9% (n = 932) were normothermic or mildly hypothermic (36.0–37.5°C), and 6.1% (n = 121) hyperthermic. Of those admitted to the neonatal unit, 217 (10.9%) died. For every 1°C increase in temperature, neonatal mortality decreased by 31% (aOR 0.69, 95% CI 0.59–0.82). Admission temperature <34.5°C was strongly associated with mortality (aOR 3.56, 1.87–6.79). Mild hypothermia (36.0–36.5°C) was not associated with mortality (aOR 1.30, 0.72–2.37). Risk factors for hypothermia were bag and mask ventilation (aOR 2.53, 2.07–3.11) and low birth weight. The introduction of radiant warmers from 1 May 2022 was associated with a decrease in hypothermia (aOR 0.54, 0.41–0.72). Conclusion Hypothermia is prevalent even in tropical settings and maintaining normothermia after birth is critical and achievable for reducing neonatal mortality.

• Reali, Laura; Onorati, Lorenza; Koletzko, Berthold; Størdal, Ketil; Aparicio Rodrigo, Maria & Magendie, Christine [Show all 9 contributors for this article] (2024). EAP and ECPCP urge ban on novel nicotine- (NNCPS) and non-nicotine-containing products (NNDS) to youth. Acta Paediatrica. ISSN 0803-5253. 113, p. 2354–2362. doi: 10.1111/apa.17358. Full text in Research Archive Show summary

  Aim We want to verify the correlation between the increasing use of novel nicotine-containing products (NNCPs) and non-nicotine delivery products (NNDPs) among young individuals and the escalating negative health consequences, necessitating their prohibition. Methods We performed a comprehensive analysis of the most relevant literature about the utilisation of NNCPs and NNDPs among young individuals and their health effects. Results Despite being initially seen as less harmful alternatives, for smokers aiming to quit, these products have become more popular due to misleading marketing claims. Teenagers using NNCPs and NNDPs, despite having no smoking history, are more likely to transition to tobacco smoking. Consistent use can lead to health issues like pulmonary damage, asthma, and cardiovascular and ocular problems. Conclusion The EAP and the ECPCP endorse the WHO's appeal to outlaw these hazardous products. They urge European governments to forbid the sale of NNCPs and NNDPs to children and adolescents in order to safeguard their well-being. They also propose specific recommendations (box 4) to support this cause.

• Kurppa, Kalle; Mulder, Chris J.; Størdal, Ketil & Kaukinen, Katri (2024). Celiac Disease Affects 1% of Global Population—Who Will Manage All These Patients? What Are Criteria to Prioritize Along Risk for Complications? Gastroenterology. ISSN 0016-5085. 167(1), p. 148–158. doi: 10.1053/j.gastro.2023.12.026. Full text in Research Archive Show summary

  Celiac disease is a common gastrointestinal condition with an estimated global prevalence of up to 1%. Adequate long-term surveillance of patients is imperative to ensure strict adherence to treatment with a gluten-free diet and the ensuing clinical and histologic recovery. Traditionally, this has been accomplished by means of regular on-site attendance at specialist health care facilities, accompanied for most patients by follow-up endoscopic and laboratory tests. However, the rapidly increasing prevalence of celiac disease and the limited health care resources challenge the current centralized and nonindividualized follow-up strategies. The improved noninvasive surveillance tools and online health care services are further changing the landscape of celiac disease management. There is a clear need for more personalized and on-demand follow-up based on early treatment response and patient-related factors associated with long-term prognosis. Additional scientific evidence on the optimal implementation of follow-up for pediatric and adulthood celiac disease is nevertheless called for.

• Andersen, Svend; Hestetun, Sigrid Valen; Bernklev, Tomm; Perminow, Gøri Margrete & Størdal, Ketil (2024). Fetal and Early-Life Antibiotics and Risk of Pediatric Inflammatory Bowel Disease: A Population-Based Nationwide Register Study. The Journal of Pediatrics: Clinical Practice. 12, p. 1–8. doi: 10.1016/j.jpedcp.2024.200096. Full text in Research Archive Show summary

  To assess whether antibiotic exposure prenatally and before 2 years of age is associated with subsequent pediatric inflammatory bowel disease (PIBD), as earlier studies diverge substantially in risk estimations or do not include prenatal exposure. Methods We performed a register-based cohort study including all children in Norway born 2004-2012 until study’s end on December 31, 2020. Exposures were defined as dispensed antibiotics to mothers during pregnancy and to children before 2 years of age. Main outcome was International Classification of Diseases, Tenth Revision, code registrations consistent with PIBD. Results Among 536 819 children, 797 PIBD cases were identified. The aOR for developing PIBD if exposed to antibiotics before 2 years of age compared with no exposure was 1.33 (95% CI 1.15-1.53), adjusted for sex and prenatal antibiotic exposure. An adjustment for maternal smoking during pregnancy increased the aOR to 1.42 (1.22-1.66), but with minimal changes after further adjustments for potential confounders related to pregnancy, birth, or socioeconomic status. A dose-response association was observed in those receiving more than 2 antibiotic courses (aOR 1.47, 1.25-1.73), and with greater effect estimates for broad-spectrum antibiotics (aOR 2.57, 1.82-3.63). Antibiotic exposure during pregnancy was numerically but not significantly associated with offspring PIBD (aOR 1.15, 0.99-1.34). Conclusions Children exposed to antibiotics before 2 years of age were more likely to develop pediatric IBD than controls. Exposure prenatally to maternal antibiotics was numerically but not statistically significant associated to subsequent PIBD.

• Thomassen, Rut Anne; Kvammen, Janne Anita; Bentsen, Beint Sigmund; Solheim, Anna; Størdal, Ketil & Henriksen, Christine [Show all 7 contributors for this article] (2024). Impact of parenteral nutrition on quality of life, the family and gastrointestinal symptoms in children with intestinal failure. Journal of Pediatric Gastroenterology and Nutrition - JPGN. ISSN 0277-2116. 80(1), p. 69–79. doi: 10.1002/jpn3.12411. Full text in Research Archive Show summary

  Objectives Intestinal failure (IF) and dependency on parenteral nutrition (PN) are risk factors for lower health-related quality of life (HRQOL) in children. Weaning from PN is a major goal of paediatric IF treatment, however, its impact on HRQOL remains unclear. This study aimed to assess HRQOL, gastrointestinal (GI) symptoms and family impact in children with IF in relation to their need for PN. Method Data were collected in a cross-sectional study from children with IF and a reference group of healthy children using electronic versions of Paediatric Quality of Life Inventory™ forms. Results The study included 56 children with IF and 48 healthy children. Parents of children with IF reported significantly lower HRQOL than healthy children (−8.7, p = 0.001). PN dependency did not influence HRQOL scores, but families with children dependent on PN had a lower family impact score than children weaned from PN (49.9 vs. 73.6, p < 0.001). Parents of children in the PN group reported more GI problems than those in the weaned group (−8.1, p = 0.04), and diarrhoea, gas and bloating were common symptoms of IF. GI symptoms varied according to PN dependency and IF aetiology. Multivariate analysis found a significant association between HRQOL and total GI symptom score (parent scores: 0.34, p = 0.02, self-score 0.48, p = 0.02). Conclusion Children with IF had lower parent-reported HRQOL than healthy children. PN dependency did not affect HRQOL, however, the need for PN had a significant negative impact on family well-being. GI symptoms may negatively impact HRQOL in the IF population.

• Bøås, Håkon; Havdal, Lise Beier; Størdal, Ketil; Døllner, Henrik; Leegaard, Truls Michael & Bekkevold, Terese [Show all 14 contributors for this article] (2024). No association between disease severity and respiratory syncytial virus subtypes RSV-A and RSV-B in hospitalized young children in Norway. PLOS ONE. 19(3). doi: 10.1371/journal.pone.0298104. Full text in Research Archive Show summary

  Objective There is conflicting evidence whether subtypes of Respiratory syncytial virus have different seasonality or are differentially associated with clinical severity. We aimed to explore the associations between disease severity and RSV subtypes RSV-A and RSV-B and to describe the circulation of RSV subtypes pattern by season and age. Methods Active prospective hospital surveillance for RSV-A and RSV-B in children <59 months of age was conducted during 2015–2018. All febrile children 12–59 months of age were enrolled, whereas children <12 months were eligible if presenting with fever or respiratory symptoms. Risk factors and upper and lower respiratory tract infection was identified by linkage to national registry data and analyzed using penalized maximum likelihood logistic regression. Results Both RSV-A and B were found to co-circulate throughout all three study seasons, and no clear seasonal pattern was identified. Likewise, we found no association between sex or measures of severity with RSV-A or RSV-B. There was significantly more RSV-A than RSV-B among children with comorbidities. Conclusions No association was found between disease severity or sex and RSV subtypes RSV-A and RSV-B in hospitalized young children in Norway.

• Lerchova, Tereza; Størdal, Ketil; Andersson, Björn; Ludvigsson, Johnny & Mårild, Karl Staffan (2024). Atopic Dermatitis in Early Childhood and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study. Journal of Pediatrics. ISSN 0022-3476. 270. doi: 10.1016/j.jpeds.2024.114027. Full text in Research Archive Show summary

  Objective To examine the association between early-life atopic manifestations and later risk of inflammatory bowel disease (IBD), for which prospective data are scarce. Study design The population-based All Babies in Southeast Sweden (ABIS) and Norwegian Mother, Father, and Child (MoBa) cohorts follow children from birth (ABIS 1997-1999; MoBa 2000-2009) to the end of 2021. Based on validated questionnaires, parents prospectively reported information on asthma, food-related allergic symptoms, atopic dermatitis, and allergic rhinitis by age 3. IBD was defined by ≥ 2 diagnostic records in the national health registries. Cox regression estimated hazard ratios adjusted (aHRs) for parental IBD, atopy, education level, smoking habits, and national origin. Cohort-specific estimates were pooled using a random-effects model. Results We compiled data on 83 311 children (ABIS, n = 9041; MoBa, n = 74 270). In over 1 174 756 person-years of follow-up, 301 participants were diagnosed with IBD. Children with atopic dermatitis at age 3 had an increased risk of IBD (pooled aHR = 1.46 [95% CI = 1.13-1.88]), Crohn's disease (pooled aHR = 1.53 [95%CI = 1.04-2.26]), and ulcerative colitis (pooled aHR = 1.78 [95%CI = 1.15-2.75]). Conversely, any atopic manifestation by age 3 was not associated with IBD (pooled aHR = 1.20 [95%CI = 0.95-1.52]), nor were analyses specifically focused on early-life food-related allergic symptoms, asthma, and allergic rhinitis. Conclusion While atopic manifestations in early childhood were overall not associated with IBD, children with atopic dermatitis specifically were at increased risk of developing IBD, suggesting shared etiologic traits; these findings might be useful in identifying at-risk individuals for IBD.

• Mårild, Karl Staffan; Lerchova, Tereza; Östensson, Malin; Imberg, Henrik; Størdal, Ketil & Ludvigsson, Johnny (2024). Early-Life Infections, Antibiotics and Later Risk of Childhood and Early Adult-Onset Inflammatory Bowel Disease: Pooled Analysis of Two Scandinavian Birth Cohorts. Alimentary Pharmacology and Therapeutics. ISSN 0269-2813. p. 323–334. doi: 10.1111/apt.18358. Full text in Research Archive Show summary

  Background Childhood antibiotic use has been associated with inflammatory bowel disease (IBD), although the potential contribution of infection frequency remains uncertain. Aims To explore the association between early-life infections, antibiotics and IBD development. Methods We used population-based data from ABIS (Sweden) and MoBa (Norway) cohorts following children from birth (1997–2009) until 2021. Prospectively collected questionnaires identified infection frequency (any, gastrointestinal and respiratory) and antibiotics (any, penicillin and non-penicillin) until age 3. IBD diagnosis required ≥ 2 records in national health registries. Cohort-specific hazard ratios (aHR), adjusted for parental education, smoking and IBD were estimated and pooled using a random-effects model. Antibiotic analyses were adjusted for infection frequency. Results There were 103,046 children (11,872 ABIS and 91,174 MoBa), contributing to 1,663,898 person-years of follow-up, during which 395 were diagnosed with IBD. The frequency of any infection at 0 to < 1 and 1 to < 3 years showed a pooled aHR of 1.01 (95% confidence interval [CI] = 0.96–1.07) and 1.00 (95% CI = 0.99–1.01) per additional infection for IBD. Adjusting for infections, any versus no antibiotics in the first year was associated with IBD (pooled aHR = 1.33 [95% CI = 1.01–1.76]). The aHR for additional antibiotic course was 1.17 (95% CI = 0.96–1.44), driven by penicillin (per additional course, aHR = 1.28 [95% CI = 1.02–1.60]). Although antibiotics at 1 to < 3 years did not show an association with IBD or Crohn's disease, non-penicillin antibiotics were associated with ulcerative colitis (per additional course, aHR = 1.95 [95% CI = 1.38–2.75]). Conclusion Early-life antibiotic use was, a significant risk factor for childhood and early adult-onset IBD, independent of infection frequency.

• Kivelä, Laura; Atneosen-Åsegg, Monica; Iversen, Marie Hellan; Kahrs, Christian Riddervold & Størdal, Ketil (2024). Faecal biomarkers in children with coeliac disease: A way forward? Acta Paediatrica. ISSN 0803-5253. doi: 10.1111/apa.17478. Full text in Research Archive Show summary

  Aim Novel markers to reflect the intestinal damage in coeliac disease are needed. We studied the potential of faecal and serum neopterin, and faecal myeloperoxidase, human β-defensin-2, and lipocalin-2 in a case–control study. Methods Data were collected from medical records and a biobank including newly diagnosed coeliac disease patients, potential coeliac disease patients and non-coeliac controls. Commercially available ELISA assays were used for measuring the biomarkers. Results Altogether 19 patients with coeliac disease (median age 9.0 years), 8 with potential coeliac disease (4.0 years) and 18 controls (6.5 years) were included. The highest faecal neopterin levels were seen in potential coeliac disease, followed by controls and coeliac disease (median 513 vs. 372 vs. 255 nmol/L, respectively, p = 0.016). Also, serum neopterin was highest in the potential coeliac disease group (9.8 vs. 5.5 vs. 5.9 nmol/L, p = 0.022). After age adjustment and robust variance estimation, only differences in serum neopterin remained significant. Other markers did not differ between the groups. None of the markers were significantly associated with serum transglutaminase-2 antibody levels. Conclusion Differences in neopterin levels amongst patients with potential coeliac disease, coeliac disease, and controls suggest that neopterin might serve as an early disease marker.

• Kivelä, Laura; Lindfors, Katri; Lundin, Knut & Størdal, Ketil (2024). Review article: Faecal biomarkers for assessing small intestinal damage in coeliac disease and environmental enteropathy. Alimentary Pharmacology and Therapeutics. ISSN 0269-2813. 60(8), p. 988–1004. doi: 10.1111/apt.18234. Full text in Research Archive Show summary

  Background In coeliac disease and environmental enteropathy, dietary gluten and enteric infections cause reversible inflammation and morphological changes to the small intestinal mucosa that can be detected in biopsy samples obtained by endoscopy. However, there is a clear need for non-invasive biomarkers. Constant shedding of mucosal material into the bowel lumen and faeces, together with easy availability of stool, makes it an interesting sample matrix. Aims To conduct a systematic literature search and summarize the existing evidence for host mucosa-derived faecal biomarkers in evaluating small intestinal damage. Methods We searched for studies on PubMed (MEDLINE) until 1 March 2024. Results We identified 494 studies and included 35 original case–control and cohort studies. These assessed host mucosal transcripts and 14 other markers aiming specifically to reflect inflammation and cell-mediated, innate and gluten-induced immune responses. In coeliac disease, faecal calprotectin and anti-gliadin, tissue transglutaminase, endomysium and deamidated gliadin peptide antibodies were the most studied but with inconsistent results. Single studies reported positive findings about microRNA transcripts, β-defensin-2, lipocalin-2, zonulin-related proteins and angiotensin-converting enzyme. In environmental enteropathy, a non-significant association was reported between calprotectin and urine lactulose/mannitol ratio; there were conflicting results for neopterin, myeloperoxidase and host transcripts. Single studies reported a positive association for lactoferrin, and a negative association for regenerating islet-derived protein 1. Studies comparing faecal markers against small intestinal biopsy findings were not identified in environmental enteropathy. Conclusions Further studies are needed to determine reliable faecal markers as a proxy for small intestinal mucosal damage.

• Larsen, Johanne Hartwedt; Andersen, Svend; Perminow, Gøri Margrete; Mundal, Håkon S.; Mårild, Karl Staffan & Stabell, Niklas [Show all 7 contributors for this article] (2024). Higher incidence of paediatric inflammatory bowel disease by increasing latitude in Norway, but stable incidence by age. Acta Paediatrica. ISSN 0803-5253. 113(7), p. 1720–1727. doi: 10.1111/apa.17222. Full text in Research Archive Show summary

  Aim To examine possible geographical and temporal differences in the incidence of childhood-onset inflammatory bowel disease (IBD) in Norway, motivated by previous research indicating relevant environmental factors explaining changing epidemiology. Methods We analysed data from children born in Norway from 2004 to 2012 (n = 541 036) in a registry-based nationwide study. After validating registry diagnoses against medical records, we defined IBD as ≥2 entries of International Classification of Diseases, 10th revision (ICD-10) codes K50, K51 and K52.3 in the Norwegian Patient registry. We estimated hazard ratios (HR) for IBD across four geographical regions with a south-to-north gradient and the incidence by period of birth. Results By the end of follow-up on 31 December 2020, 799 IBD diagnoses were identified (Crohn's disease: n = 465; ulcerative colitis, n = 293, IBD: unclassified, n = 41). Compared to children in the southernmost region, there was almost a two-fold HR for IBD in children in the most Northern region (HR = 1.94, 95% Cl = 1.47–2.57; Mid region: HR = 1.68, 95% CI = 1.29–2.19, ptrend <0.001). These estimates remained largely unchanged after adjustment for potential confounding factors. The cohorts born in 2004–2006 and 2010–2012 had comparable cumulative incidences, with a slightly higher incidence for those born in 2007–2009. Conclusion We observed an increase in the risk of IBD by increasing latitude which may suggest that environmental factors influence the development of IBD, although non-causal explanations cannot be ruled out.

• Ulnes, Maria; Albrektsson, Henrik; Størdal, Ketil; Saalman, Robert; Ludvigsson, Jonas F. & Mårild, Karl Staffan (2023). Lack of Follow-Up for Celiac Disease During Childhood Not Associated With Poor Health Outcomes: A Regional Swedish Cohort Study. Journal of Pediatric Gastroenterology and Nutrition - JPGN. ISSN 0277-2116. 77(5), p. 640–647. doi: 10.1097/MPG.0000000000003911. Full text in Research Archive Show summary

  Objectives: The objective of the study is to examine the association between the lack of follow-up for celiac disease (CD) during childhood and dietary adherence, disease remission, and health-related quality of life (HRQoL). Methods: We invited 243 randomly selected children diagnosed with CD in 2013–2018 in Gothenburg, Sweden, and 162 consented to participate (67%). We retrieved information on clinical follow-up and current wellbeing using medical and laboratory records data, as well as validated questionnaires on symptoms of CD, dietary adherence, and HRQoL. We analyzed tissue-transglutaminase antibodies (tTGA) as a measure of disease remission. We defined lack of follow-up as no CD-related physician/dietician-led visit or measurement of tTGA over the past 24 months of study enrollment. Results: The mean age at study enrolment was 12.7 (range 7.8–18.2) years. Out of 162 children with an average disease duration of 5.3 (range 2.3–8.8) years, 23 (14%) lacked follow-up. tTGA had normalized in 94% [95% confidence interval (CI) = 71%–100%] of children without follow-up versus 91% (95% CI: 85%–95%) of children with continued follow-up. Of children without follow-up, 65% (95% CI: 38%–86%) reported a dietary adherence score indicating very good adherence, versus 72% (95% CI: 63%–80%) of those with continued follow-up. Also, lack of follow-up was not significantly associated with growth, symptom scores, or HRQoL. Conclusions: In this regional cohort study of mostly older children and adolescents, lack of follow-up for CD was not significantly linked to dietary adherence, disease remission, or HRQoL. How these results hold in larger, unselected samples with longer follow-up, including transition to adult care, warrants further study.

• Closs, Emilie Raaum; Mårild, Karl Staffan; Nielsen, Rasmus Gaardskær & Størdal, Ketil (2023). Use of proton pump inhibitors in scandinavian children and adolescents: An observational study. Frontiers in Pediatrics. 11. doi: 10.3389/fped.2023.1052978. Full text in Research Archive Show summary

  Aims To examine the use of proton pump inhibitors (PPIs) in Scandinavian children with focus on the geographical variation, temporal changes and possible contributing factors to observed changes. Methods An observational population-based study of children and adolescents (1-17 years) in Norway, Sweden, and Denmark during the period 2007-2020. Information concerning dispensed PPIs was obtained from the national prescription databases of each country and presented as means per 1,000 children for each country and calendar year in four age categories (1-4, 5-9, 10-13 and 14-17 years). Results In 2007, the PPI use in children was similar across Scandinavian countries. An increased PPI use was observed in all countries during the study period, with gradually increasing differences between the countries. In general, Norway showed both the largest total increase and the largest increase in each age category compared to Sweden and Denmark. In 2020 Norwegian children showed, on average, a 59% higher PPI use compared to Swedish children and a more than double the overall dispensation rate than Denmark. In Denmark there was a 19% reduction in dispensed PPIs from 2015 to 2020. Conclusion Despite being countries with similar health care systems and without indications of increased incidence of gastroesophageal reflux disease (GERD), we observed considerable geographical variation and temporal changes of PPI use in children. Although this study did not contain data on the indication for PPI use, these large differences across countries and time may indicate a current overtreatment.

• Jansen, Danielle; Brenner, Maria; Illy, Károly; Dembiński, Łukasz; Torso, Stefano del & Grossman, Zachi [Show all 13 contributors for this article] (2023). Leave no one behind: why WHO's regional office for Europe should prioritise children and adolescents in their program of work. A position statement from the European academy of paediatrics. Frontiers in Pediatrics. 11. doi: 10.3389/fped.2023.1184870. Full text in Research Archive Show summary

  Children and adolescents are no longer a priority in the most recent European Programme of Work (EPW) 2020–2025 of the World Health Organization (WHO) Regional Office for Europe. In this position statement we provide arguments for why we think this population should be explicitly addressed in this important and influential document. We firstly emphasize the persistent health problems and inequalities in access to care for children and adolescents that are challenging to solve, and thus require a continuous focus. Secondly, we urge the WHO to prioritize children and adolescents in their EPW due to the new and emerging health problems related to global issues. Finally, we explain why permanent prioritization of children and adolescents is essential for the future of children and of society.

• Hestetun, Sigrid Valen; Andersen, Svend; Sanner, Helga & Størdal, Ketil (2023). Antibiotic exposure in prenatal and early life and risk of juvenile idiopathic arthritis: a nationwide register-based cohort study. RMD Open. 9(3), p. 1–8. doi: 10.1136/rmdopen-2023-003333. Full text in Research Archive Show summary

  Objectives Early antibiotic exposure influences the gut microbiota which is believed to be involved in the pathogenesis of juvenile idiopathic arthritis (JIA). We aimed to investigate the association between systemic antibiotics in prenatal and early life and risk of JIA. Methods We conducted a register-based cohort study including all children born in Norway from 2004 through 2012. The children were followed until 31 December 2020. Main exposures were dispensed antibiotics to the mother during pregnancy and to the child during 0–24 months of age. The outcome was defined by diagnostic codes indicating JIA. Multivariate logistic regression analyses were performed to estimate the association between antibiotic exposure and JIA. Results We included 535 294 children and their mothers in the analyses; 1011 cases were identified. We found an association between exposure to systemic antibiotics during 0–24 months and JIA (adjusted OR (aOR) 1.40, 95% CI 1.24 to 1.59), with a stronger association for >1 course (aOR 1.50, 95% CI 1.29 to 1.74) vs 1 course (aOR 1.31, 95% CI 1.13 to 1.53). Subanalyses showed significant associations in all age periods except 0–6 months, and stronger association with sulfonamides/trimethoprim and broad-spectrum antibiotics. There was no association between prenatal antibiotic exposure and JIA. Conclusions The novel observation of no association with prenatal antibiotic exposure and JIA suggests that the association between antibiotics in early life and JIA is unlikely to be confounded by shared family factors. This may indicate that exposure to antibiotics in early life is an independent risk factor for JIA.

• Larsen, Vilde Bergstad; Størdal, Ketil; Telle, Kjetil Elias; Methi, Fredrik & Magnusson, Karin (2023). Health care use after severe respiratory tract infections in children aged 0 to 5 years. Scandinavian Journal of Public Health. ISSN 1403-4948. doi: 10.1177/14034948231197250. Full text in Research Archive Show summary

  Aim: To explore whether children in specialist care with COVID-19 have increased post-discharge health care use when compared with children in specialist care with 1) respiratory syncytial virus (RSV) infection, and 2) other respiratory tract infections (RTIs). Methods: In 34,214 children aged 1 month to 5 years who were registered as having one or more hospital visit (outpatient or inpatient) with a diagnosis of COVID-19 ( N = 128), RSV infection ( N = 4,009), or other RTIs ( N = 34,458) from 2017 to 2021, we used a difference-in-differences study design to investigate individual all-cause primary and specialist health care use from 12 weeks prior to 12 weeks after the hospital visit, stratified by infants (1 to 11 months) and children (1 to 5 years). Results: We found a slight increase in primary health care use in the first 4 weeks after the hospital visit for infants with COVID-19 when compared with infants with RSV infection (6 per 10,000; 95% CI [2, 13], a 0.52% relative increase). For infants diagnosed with COVID-19, we found a similar post-visit increase in inpatients when compared with infants with RSV infection, which lasted for 12 weeks. Conclusions: Our findings imply a slightly increased health care use among infants after a hospital visit for COVID-19 than among infants with other RTIs, the potential etiological mechanisms of which deserve future clinical research. Severe COVID-19 in young children will not represent any markedly increased burden on the health services.

• Lerchova, Tereza; Östensson, Malin; Sigvardsson, Ida; Størdal, Ketil; Guo, Annie & Mårild, Karl Staffan [Show all 7 contributors for this article] (2023). Physical activity in childhood and later risk of inflammatory bowel disease: A Scandinavian birth cohort study. United European Gastroenterology Journal (UEG Journal). ISSN 2050-6406. 11(9), p. 874–883. doi: 10.1002/ueg2.12469. Full text in Research Archive Show summary

  Abstract Background and Objective Retrospective data have linked adult physical activity (PA) to reduced risk of inflammatory bowel disease (IBD). We aimed to prospectively examine the association of PA and screen time (ST) in childhood with later risk of IBD, for which data are scarce. Methods Using two population‐based birth cohorts (All Babies in Southeast Sweden [ABIS] and Norwegian Mother, Father, and Child Cohort Study [MoBa]), we retrieved parent‐reported data on PA and ST degree at ages 3 and 8 years. Data were modelled as binary (high vs. low) and numerical (hours/day) exposures. Inflammatory bowel disease was defined as ≥2 diagnostic records in national health registers. Cox regression estimated hazard ratios adjusted for potential confounding from parental IBD, country of origin, education, and smoking habits (Adjusted hazard ratio (aHR)). Our 8‐year analyses included a 2‐year lag period to reduce the risk of reverse causation. Cohort‐specific estimates were pooled using random‐effects model. Result Among 65,978 participants from ABIS ( n  = 8810) and MoBa ( n  = 57,168) with available data, 266 developed IBD. At 3 years, children with high versus low PA had an aHR of 1.12 for IBD (95%CI = 0.87–1.43); high versus low ST showed an aHR of 0.91 (95%CI = 0.71–1.17). Conversely, at 8 years, high versus low ST was associated with increased risk of later IBD (aHR = 1.51; 95%CI = 1.02–2.25), but PA at 8 years, was not linked to IBD (aHR = 1.19; 95%CI = 0.80–1.76). Subtype‐specific analyses for Crohn's disease and ulcerative colitis did not differ appreciably. Conclusion Acknowledging possible confounding variables, children with high versus low ST at 8 years were at increased risk of IBD. In contrast, PA degree was not linked to IBD at any age category.

• Aasen, Eline R. Hildursdotter Vatne; Søvik, Marte Løvaas; Størdal, Ketil & Lee, Anja (2023). Are We on the Same Page? Exploring Pediatric Patients’ Involvement With Advance Care Planning. Journal of Pain and Symptom Management. ISSN 0885-3924. 66(3), p. 353–363. doi: 10.1016/j.jpainsymman.2023.04.003. Full text in Research Archive Show summary

  Background According to the UN Convention on the Rights of the Child, children have a right to be heard. This also applies to patients in pediatric palliative care (PPC). The aim of this literature review was to explore what is known about the involvement of children (<14 years of age), adolescents and young adults (AYAs) in advance care planning (ACP) in PPC. Methods A search was conducted in PubMed including publications from January 1, 2002 until December 31, 2021. The identified citations had to report on ACP or related terms in any PPC context. Results A total of n = 471 unique reports were identified. Final inclusion criteria were met by n = 21 reports, including children and AYAs with diagnoses related to oncology, neurology, HIV/AIDS and cystic fibrosis. Nine reports were from randomized controlled studies, investigating ACP methodology. The main findings were: 1) caregivers are included more often than children and adolescents in ACP, 2) some studies indicate an incongruence between AYAs and their caregivers regarding ACP and treatment preferences, 3) although the process evokes a wide range of emotions, ACP is perceived as helpful by many AYAs Conclusion The majority of studies about ACP in PPC do not include children and AYAs. Whether incongruence reported in some studies between AYAs and their caregivers regarding treatment preferences could be reduced by ACP should be further explored, including the involvement of children and adolescents in ACP, and the impact of pediatric ACP on patient outcomes in PPC.

• Rydland, Eva; Høye, Sigurd & Størdal, Ketil (2023). Antibiotic use for airway infections in Norwegian children—A national register-based study. Acta Paediatrica. ISSN 0803-5253. 113(3), p. 537–543. doi: 10.1111/apa.17052. Full text in Research Archive Show summary

  Abstract Aim Respiratory tract infections (RTIs) are major contributors to childhood antibiotic use. We aimed to investigate geographical and temporal trends in the prescription of antibiotics and consultations for RTIs in children &lt;18 years living in Norway from 2010 to 2017. Methods In a nationwide observational study, we analysed antibiotic prescriptions from the Norwegian Prescription Database and reimbursed contacts from primary care physicians. We limited the study to airway antibiotics and diagnostic codes indicating RTIs. Results Antibiotic prescriptions due to an RTI varied from 75 to 134 per 1000 consultation due to RTI across counties in Norway (relative risk 1.79, 95% CI 1.68–1.90 for highest compared to lowest). The use of health care varied from 414 to 585 consultations for RTI per 1000 inhabitant/year (relative risk 1.43, 95% CI 1.41–1.44 for highest compared to lowest). From 2010 to 2017, we observed a 21% reduction in antibiotic prescriptions per RTI consultation and of 6% for the number of consultations for an RTI. At the county level, the use of health care was positively associated with the proportion of RTIs that resulted in antibiotic prescription. Conclusion We found a reduction in doctors' antibiotic prescription and the use of health care for RTIs, and a variation across counties.

• Rossholt, Madelaine; Bratlie, Marianne; Wendel, Kristina; Aas, Marlen Fossan; Gunnarsdottir, Gunnþórunn & Fugelseth, Drude [Show all 11 contributors for this article] (2023). Effect of arachidonic and docosahexaenoic acid supplementation on quality of growth in preterm infants: A secondary analysis of a randomized controlled trial. Clinical Nutrition. ISSN 0261-5614. 42(12), p. 2311–2319. doi: 10.1016/j.clnu.2023.10.005. Full text in Research Archive Show summary

  Background & aims A balanced supply of arachidonic acid (ARA) and docosahexaenoic acid (DHA) may be crucial for quality of growth in preterm infants. This secondary analysis of a randomized controlled trial aimed to determine the effect of enhanced ARA and DHA supplementation on growth and body composition in infants born before 29 weeks of gestation. Furthermore, we aimed to study associations between human milk feeding, growth patterns and body composition. Methods The ImNuT-trial randomized 121 infants to receive a daily supplement with medium chain triglycerides (control) or 100 mg/kg ARA and 50 mg/kg DHA (ARA:DHA group) from the second day of life until 36 weeks postmenstrual age. Growth and body composition were evaluated up to 3 months corrected age. Results The ARA:DHA group showed better linear growth from birth to term equivalent age compared to the control group; mean difference in z score change from birth for length was 0.74 ([95% CI, 0.17–1.3]; p = 0.010). There were no differences in growth and body composition outcomes at 3 months corrected age between the groups. An increase in z score for weight after 36 weeks postmenstrual age and breastfeeding at 3 months corrected age were the strongest positive predictors of fat mass% at 3 months corrected age (both, p < 0.001). Conclusion Early enhanced supplementation of ARA and DHA may be beneficial with respect to somatic growth in very preterm infants.

• Størdal, Ketil; Tapia, German; Lund-Blix, Nicolai Andre & Stene, Lars Christian Mørch (2023). Genotypes predisposing for celiac disease and autoimmune diabetes and risk of infections in early childhood. Journal of Pediatric Gastroenterology and Nutrition - JPGN. ISSN 0277-2116. 78(2), p. 295–303. doi: 10.1002/jpn3.12078. Full text in Research Archive Show summary

  Abstract Objectives Infections in early childhood have been associated with risk of celiac disease (CD) and type 1 diabetes (T1D). We investigated whether this is driven by susceptibility genes for autoimmune disease by comparing infection frequency by genetic susceptibility variants for CD or T1D. Methods We genotyped 373 controls and 384 children who developed CD or T1D in the population‐based Norwegian Mother, Father and Child Cohort study (MoBa) study for human leukocyte antigen (HLA)‐DQ, FUT2, SH2B3 , and PTPN22 , and calculated a weighted non‐HLA genetic risk score (GRS) for CD and T1D based on over 40 SNPs. Parents reported infections in questionnaires when children were 6 and 18 months old. We used negative binomial regression to estimate incidence rate ratio (IRR) for infections by genotype. Results HLA genotypes for CD and T1D or non‐HLA GRS for T1D were not associated with infections. The non‐HLA GRS for CD was associated with a nonsignificantly lower frequency of infections (aIRR: 0.95, 95% CI: 0.87−1.03 per weighted allele score), and significantly so when restricting to healthy controls (aIRR: 0.89, 0.81−0.99). Participants homozygous for rs601338(A;A) at FUT2 , often referred to as nonsecretors, had a nonsignificantly lower risk of infections (aIRR: 0.91, 95% CI: 0.83−1.01).  SH2B3 and PTPN22 genotypes were not associated with infections. The association between infections and risk of CD (OR: 1.15 per five infections) was strengthened after adjustment for HLA genotype and non‐HLA GRS (OR: 1.24). Conclusions HLA variants and non‐HLA GRS conferring susceptibility for CD were not associated with increased risk of infections in early childhood and is unlikely to drive the observed association between infections and risk of CD or T1D in many studies.

• Rossholt, Madelaine; Bratlie, Marianne; Wendel, Kristina; Aas, Marlen Fossan; Gunnarsdottir, Gunnþórunn & Fugelseth, Drude [Show all 10 contributors for this article] (2023). A standardized feeding protocol ensured recommended nutrient intakes and prevented growth faltering in preterm infants < 29 weeks gestation. Clinical Nutrition ESPEN. ISSN 2405-4577. 53, p. 251–259. doi: 10.1016/j.clnesp.2022.12.024. Full text in Research Archive Show summary

  Background & aims Nutrition is a cornerstone of postnatal care to prevent compromised growth and support short- and long-term health outcomes in preterm infants. We aimed to evaluate nutritional intakes and growth among infants <29 weeks gestation after implementation of a standardized feeding protocol. Methods This is an observational cohort secondary analysis of data from the ImNuT study (Immature, Nutrition Therapy, NCT03555019). To reduce variations in nutritional practice and ensure accommodation to current guidelines, we developed a standardized feeding protocol. Detailed information on actual nutritional intakes, growth and biochemistry was prospectively collected and assessed from birth to 36 weeks postmenstrual age (PMA). Results Median (range) gestational age and birth weight were 26+6 (22+6-28+6) weeks and 798 (444–1485) g. Energy and macronutrient intakes progressively increased from birth through transition to exclusive enteral feeds. Parenteral nutrition was weaned at median (IQR) day 11 (9, 14) when nutritional requirements were met by exclusively enteral feeds. Infants exhibited a median (IQR) weight loss of 7.8% (5.7, 11.6) and regained birth weight by day 8 (7, 11). Average velocity in weight, length and head circumference from birth to 36 weeks PMA were in accordance with target growth rates; median (IQR) 15.8 (14.7, 17.7) g/kg/d, 1.1 (0.98, 1.3) cm/week and 0.82 (0.83, 0.89) cm/week. At 36 weeks PMA, only 3% of infants exhibited moderate growth faltering (decline in weigh-for-age z score >1.2 from birth), and none severe. Conclusions In infants <29 weeks gestation, the standardized feeding protocol was well tolerated. Nutrient intakes and growth were close to recommendations.

• Rossholt, Madelaine; Wendel, Kristina; Bratlie, Marianne; Aas, Marlen Fossan; Gunnarsdottir, Gunnþórunn & Fugelseth, Drude [Show all 11 contributors for this article] (2023). Vitamin A Status in Preterm Infants Is Associated with Inflammation and Dexamethasone Exposure. Nutrients. 15(2). doi: 10.3390/nu15020441. Full text in Research Archive Show summary

  Vitamin A has a key role in lung development and its deficiency is associated with an increased risk of bronchopulmonary dysplasia. This secondary cohort analysis of the ImNuT trial (Immature, Nutrition Therapy NCT03555019) aimed to (1) explore vitamin A status in preterm infants &lt;29 weeks gestation and (2) assess the influence of inflammation and postnatal dexamethasone exposure on vitamin A concentrations in blood. We report detailed information on vitamin A biochemistry, vitamin A intake, markers of inflammation and dexamethasone exposure. After four weeks of age, infants exposed to dexamethasone (n = 39) showed higher vitamin A concentrations compared to unexposed infants (n = 41); median (IQR) retinol was 1.0 (0.74, 1.5) vs. 0.56 (0.41, 0.74) µmol/L, p &lt; 0.001. Pretreatment retinol concentrations were lower in the dexamethasone group compared to non-exposed infants (p &lt; 0.001); 88% vs. 60% of the infants were considered deficient in vitamin A (retinol &lt; 0.7 µmol/L) at one week of age. Small size for gestational age, mechanical ventilation and elevated levels of interleukin-6 were factors negatively associated with first-week retinol concentrations. In conclusion, preterm infants &lt;29 weeks gestation are at risk of vitamin A deficiency despite intakes that accommodate current recommendations. The presence of inflammation and dexamethasone exposure should be considered when interpreting vitamin A status.

• Guo, Annie; Östensson, Malin; Størdal, Ketil; Ludvigsson, Johnny & Mårild, Karl (2023). Early-Life Hygiene-Related Factors and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study. Inflammatory Bowel Diseases. ISSN 1078-0998. 30(10), p. 1820–1830. doi: 10.1093/ibd/izad257. Full text in Research Archive Show summary

  Abstract Background We aimed to investigate whether early-life hygiene-related factors influenced the risk of inflammatory bowel disease (IBD) in a Scandinavian population and test the association’s consistency across cohorts. Methods This study followed 117 493 participants in the All Babies in Southeast Sweden study and the Norwegian Mother, Father, and Child Cohort Study. IBD diagnoses were defined by national registers. Comprehensive data on hygiene-related exposures, such as having pets, rural living, daycare attendance, and siblings, were retrieved from questionnaires administered from pregnancy until child’s age of 36 months. A multivariable Cox regression model yielded adjusted hazard ratios (aHRs) for IBD accounting for socioeconomic status and perinatal factors. Cohort-specific estimates were pooled using a random-effects model. Results In over 2 024 299 person-years of follow-up 451 participants developed IBD. In pooled estimates children attending daycare up to 36 months of life vs not attending daycare were less likely to develop Crohn’s disease (aHR, 0.60; 95% confidence interval [CI], 0.37- 0.98). Children having 1 or more siblings had a modestly increased risk of IBD (aHR, 1.17; 95% CI, 0.96-1.42; aHR for each sibling, 1.12; 95% CI, 1.01-1.24). The other hygiene factors were not significantly linked to later IBD. In the Norwegian Mother, Father, and Child Cohort Study cohort, bed sharing was associated with an increased risk of IBD, most notably for ulcerative colitis (aHR, 1.67; 95% CI, 1.01-2.78). Conclusions In this birth cohort study from 2 high-income Scandinavian countries, some early-life hygiene-related exposures were associated with IBD risk. The generalizability of these results to countries of other socioeconomic level is unknown.

• Sigvardsson, Ida; Størdal, Ketil; Östensson, Malin; Guo, Annie; Ludvigsson, Johnny & Mårild, Karl (2023). Childhood Socioeconomic Characteristics and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study. Inflammatory Bowel Diseases. ISSN 1078-0998. 30(10), p. 1801–1811. doi: 10.1093/ibd/izad220. Full text in Research Archive Show summary

  Abstract Background Ecological observations suggest a negative relationship between childhood socioeconomic status (SES) and inflammatory bowel disease (IBD) risk. Individual-level analyses have been inconsistent and mostly lacked refined assessments of SES. We aimed to comprehensively study the association between early-life SES and later IBD. Methods This study included 117 493 participants from the Norwegian Mother, Father and Child cohort and Swedish All Babies in Southeast Sweden cohorts. Participants were followed from birth (1997-2009) through 2021. IBD was identified through national patient registers. Questionnaire and register data were used to define parental educational level, employment, and household income level. Cox regression estimated adjusted hazard ratios (aHRs), accounting for other SES exposures and covariates (eg, parental IBD). Cohort-specific estimates were pooled using a random-effects model. Results During 2 024 299 person-years of follow-up, 451 participants were diagnosed with IBD (All Babies in Southeast Sweden cohort, n = 113 and Norwegian Mother, Father and Child cohort, n = 338). Early-life maternal, but not paternal, educational level was associated with later IBD (low vs high educational level; pooled aHR, 1.81; 95% confidence interval [CI], 1.16-2.82; and pooled aHR, 1.20; 95% CI, 0.80-1.80; respectively). Having a nonworking mother or father was not significantly associated with IBD (pooled aHR, 0.69; 95% CI, 0.47-1.02; pooled aHR, 0.79; 95% CI, 0.45-1.37). High vs low household income level yielded a pooled aHR of 1.33 (95% CI, 0.94-1.89). Overall, results were largely consistent across cohorts. Conclusions In this prospective Scandinavian cohort study, low maternal educational level was, independent of other SES and covariates, significantly associated with later IBD in her child. Further research is needed to elucidate factors that may mediate this relationship.

• Landaas, Vibeke Østberg; Skjerven, Håvard Ove; Carlsen, Karin Cecilie Lødrup; Størdal, Ketil & Håland, Geir (2023). Home-Based Double-Blind, Placebo-Controlled Challenges for Diagnosis of Delayed Gluten/Milk Hypersensitivity in Children. Journal of Allergy and Clinical Immunology: In Practice. ISSN 2213-2198. 12(3), p. 652–659. doi: 10.1016/j.jaip.2023.12.032. Full text in Research Archive
• Östensson, Malin; Björkqvist, Olle; Guo, Annie; Størdal, Ketil; Halfvarson, Jonas & Mårild, Karl [Show all 7 contributors for this article] (2023). Epidemiology, validation, and clinical characteristics of inflammatory bowel disease: the ABIS birth cohort study. BMC Gastroenterology. 23, p. 1–9. doi: 10.1186/s12876-023-02840-1. Full text in Research Archive Show summary

  Background Birth cohort studies with linked register-based data on inflammatory bowel disease (IBD) provide opportunities to prospectively study early-life determinants of the disease. However, register-based data often lack information on clinical characteristics and rely on diagnostic algorithms. Within the All Babies in Southeast Sweden (ABIS) cohort, we examined the validity of a register-based definition of IBD, its incidence, and clinical and therapeutic characteristics at diagnosis. Methods We followed 16,223 children from birth (1997–1999) until the end of 2020 for the diagnosis of IBD as defined by a minimum of two diagnostic codes for IBD in the Swedish National Patient Register (NPR). We described the incidence and cumulative incidence of IBD. Through a medical record review of cases diagnosed by the end of 2017, we examined the positive predictive value (PPV) for IBD and described its clinical characteristics and treatment. Results By 2020, at an average age of 22.2 years, 113 participants (0.74%, 95% confidence interval [CI] = 0.61–0.89) had a register-based diagnosis of IBD, corresponding to an incidence of 31.3 per 100,000 person-years of follow-up; the incidence for Crohn’s disease (CD) was 11.1 per 100,000 person-years and 15.8 for ulcerative colitis (UC). Of 77 participants with a register-based definition of IBD by the end of 2017, medical records were identified for 61 participants, of whom 57 had true IBD (PPV = 93%; 95%CI = 0.87–1.00). While oral 5-aminosalicylic acid treatment was equally common in newly diagnosed CD and UC patients, biologics were more often used for newly diagnosed CD. The median faecal calprotectin levels were 1206 mg/kg at diagnosis and 93 mg/kg at the last follow-up (P < 0.001). Conclusions In this population-based sample of Swedish children and young adults the cumulative IBD incidence was 0.74. The validity of register-based definition of IBD was high and supports using such data to identify IBD patients in cohort studies.

• Closs, Emilie Raaum; Lyamouri, Miriam; Øymar, Knut Asbjørn Alexander & Størdal, Ketil (2023). Regionale forskjeller i bruk av protonpumpehemmere hos barn. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(9), p. 782–787. doi: 10.4045/tidsskr.22.0771. Full text in Research Archive Show summary

  Bakgrunn: Fysiologisk gastroøsofageal refluks i spedbarnsalder er vanskelig å skille fra reflukssykdom. Internasjonale retningslinjer anbefaler restriktiv bruk av syrehemmende behandling til spedbarn på grunn av mangel på dokumentert effekt, men for både spedbarn og eldre barn har bruken økt de siste åra. Formålet med studien er å beskrive endring over tid og geografisk variasjon i utredning og behandling for mistenkt gastroøsofageal reflukssykdom. Materiale og metode: I aggregerte data fra Legemiddelregisteret for perioden 1.1.2007–31.12.2020 undersøkte vi regionale forskjeller i antall utleveringer av protonpumpehemmere til barn og ungdom. Data fra Norsk pasientregister ble analysert for å kartlegge bruken av 24-timers pH-måling og gastroskopi, som kan støtte mistanken om gastroøsofageal reflukssykdom. Resultater: Antall utleveringer av protonpumpehemmere første leveår økte, og var høyest i Helse Sør-Øst med 10,1 per 1 000 barn i 2007 og 54,7 per 1 000 barn i 2020 (relativ risiko 5,4, 95 %-konfidensintervall 4,6 til 6,4). Antall utleveringer i 2020 var 64 % høyere i Helse Sør-Øst sammenlignet med Helse Nord og Helse Midt-Norge. Antall gastroskopier endret seg lite, men bruk av 24-timers pH-måling falt med 52 % fra 2016 til 2020. Fortolkning: Bruk av protonpumpehemmere til spedbarn har økt betydelig på tross av retningslinjer. Sammen med geografisk variasjon kan dette tyde på overbehandling av fysiologisk refluks hos spedbarn. Færre utredninger tyder på at en økende andel blir behandlet uten støttende diagnostikk.

• Heen, Espen Kolstad; Størdal, Ketil; Wachira, John; Heen, Ingjerd & Lundeby, Karen Marie (2022). Do we need a new global policy for ending preventable perinatal deaths in fragile low-income countries? Journal of Global Health. ISSN 2047-2978. 12. doi: 10.7189/jogh.12.03020. Full text in Research Archive
• Heen, Espen Kolstad; Størdal, Ketil; Abdi, Abdirashid; Walmann, Frøydis & Lundeby, Karen Marie (2022). Facility-based care of small and sick newborns: experiences with establishing a neonatal special care unit in Somaliland. Journal of Global Health Reports (JoGHR). 6. doi: 10.29392/001c.33619. Full text in Research Archive Show summary

  Background The goal of the United Nations is a global neonatal mortality rate (NMR) lower than 12/1000 by 2030. In stark contrast, facility-based care of small and sick newborns is limited and substandard in many low-income countries (LIC). There is a need to identify broad packages of high-quality and low-cost, sustainable interventions suitable for scale-up in fragile states and high burden countries. This article describes the process, output, and experience of establishing a neonatal special care unit (NSCU) at a governmental hospital in Somaliland. Methods We collected data from administrative documents, staff experiences, patient registries, and primary caretaker interviews covering 164 admissions through 5 months and systematized the findings within the 6 building blocks of the health care system (WHO). Results Running an NSCU in a Somali context is both possible and feasible when implementers are willing to bridge gaps on all health systems building blocks simultaneously. A verified NSCU survival rate of 85% within the first year was achieved - in line with reputable neonatal wards in the wider Eastern Africa. General caretaker satisfaction was rated as “good.” Major challenges were lack of a national regulatory framework, including an effective funding allocation; staff unfamiliarity with detailed guidelines, protocols, and job descriptions; and poor availability of medicines and other neonatal disposables. For less than US$175 in running cost per patient, including staff salaries and major equipment replacements, 75% of small and sick newborns received admission-to-discharge curative care. Public demand for facility-based newborn care was quickly growing during the implementation phase. Neonatal nurses quickly drift to nongovernmental and urban employers without a persistent and deliberate overcapacity in training courses and a strong public retention policy. A 100% service coverage in Somaliland will require dedicated wards (NSCU) with equipment at all hospitals with a labor ward, and training and deployment of about 400 neonatal nurses. Conclusions The described package of interventions may have the potential for further scale-up to district hospitals in Somaliland. Policymakers and hospital administrators should strive for a stronger national regulatory, administrative, and technical framework in neonatal curative care, facilitating the simultaneous development of all of WHO’s 6 health systems building blocks. We expect many of the findings to be transferable to the wider Somalia and other fragile LIC.

• Dewez, Juan Emmanuel; Pembrey, Lucy; Nijman, Ruud G.; Torso, Stefano del; Grossman, Zachi & Hadjipanayis, Adamos [Show all 54 contributors for this article] (2022). Availability and use of rapid diagnostic tests for the management of acute childhood infections in Europe: A cross-sectional survey of paediatricians. PLOS ONE. 17(12). doi: 10.1371/journal.pone.0275336. Full text in Research Archive Show summary

  Background Point-of-care-tests (POCTs) have been advocated to optimise care in patients with infections but their actual use varies. This study aimed to estimate the variability in the adoption of current POCTs by paediatricians across Europe, and to explore the determinants of variability. Methods and findings A cross-sectional survey was conducted of hospital and primary care paediatricians, recruited through professional networks. Questions focused on the availability and use of currently available POCTs. Data were analysed descriptively and using Median Odds Ratio (MOR) to measure variation between countries. Multilevel regression modelling using changes in the area under the receiver operating characteristic curve of models were used to assess the contribution of individual or workplace versus country level factors, to the observed variation. The commonest POCT was urine dipsticks (UD) which were available to >80% of primary care and hospital paediatricians in 68% (13/19) and 79% (23/29) countries, respectively. Availability of all POCTs varied between countries. In primary care, the country (MOR) varied from 1.61 (95%CI: 1.04–2.58) for lactate to 7.28 (95%CI: 3.04–24.35) for UD. In hospitals, the country MOR varied from 1.37 (95%CI:1.04–1.80) for lactate to 11.93 (95%CI:3.35–72.23) for UD. Most paediatricians in primary care (69%, 795/1154) and hospital (81%, 962/1188) would use a diagnostic test in the case scenario of an infant with undifferentiated fever. Multilevel regression modelling showed that the country of work was more important in predicting both the availability and use of POCTs than individual or workplace characteristics. Conclusion There is substantial variability in the adoption of POCTs for the management of acute infections in children across Europe. To inform future implementation of both existing and innovative tests, further research is needed to understand what drives the variation between countries, the needs of frontline clinicians, and the role of diagnostic tests in the management of acute childhood infections.

• Jankauskaite, Lina; Grechukha, Yevgenii; Kjær, Kristin Avranden; Mamenko, Marina; Nakstad, Britt & Romankevych, Ivanna [Show all 13 contributors for this article] (2022). Overuse of medical care in paediatrics: A survey from five countries in the European Academy of Pediatrics. Frontiers in Pediatrics. 10, p. 1–9. doi: 10.3389/fped.2022.945540. Full text in Research Archive Show summary

  Studies and initiatives such as the “Choosing wisely” (CW) campaign emphasise evidence-based investigations and treatment to avoid overdiagnosis and overtreatment. The perception of the extent of medical overactivity among professionals and drivers behind are not well studied in the paediatric field. Aim We aimed to investigate the physicians‘ opinion and clarify the main drivers regarding medical overactivity in member countries of the European Academy of Paediatrics (EAP). Methods In this study, paediatricians, paediatric residents, primary care paediatricians, and family doctors treating children were surveyed in Norway, Lithuania, Ukraine, Italy, and Switzerland. Over-investigation was defined as “diagnostic work-up or referral that is unlikely to provide information which is relevant for a patient” and overtreatment was defined as “treatment that does not benefit or can harm more than benefit the patient.” The original questionnaire was developed in 2018 by a working group from the Norwegian Paediatric Association. Results Overall, 1,416 medical doctors participated in the survey, ranging from 144 in Lithuania to 337 in Switzerland. 83% stated that they experienced over-investigation/overtreatment, and 81% perceived this as a problem. The majority (83%) perceived expectations from family and patients as the most important driver for overtreatment in their country. Other drivers for overuse were use of national guidelines/recommendations, worry for reactions, and reduction of uncertainty. Conclusion This is the first study investigating knowledge and attitude toward medical overactivity in European countries. Despite different cultural and economic environments, the patterns and drivers of increased investigations and medicalisation are similar.

• Havdal, Lise Beier; Bøås, Håkon; Bekkevold, Terese; Kran, Anne-Marte Bakken; Rojahn, Astrid & Størdal, Ketil [Show all 15 contributors for this article] (2022). Risk factors associated with severe disease in respiratory syncytial virus infected children under 5 years of age. Frontiers in Pediatrics. 10. doi: 10.3389/fped.2022.1004739. Full text in Research Archive Show summary

  Objective: To evaluate risk factors for severe disease in children under 59 months of age hospitalized with respiratory syncytial virus (RSV) infection. Study design: We prospectively enrolled 1,096 cases of laboratory confirmed RSV infection during three consecutive RSV seasons in 2015–2018. Potential risk factors for severe disease were retrieved through patient questionnaires and linkage to national health registries. Need for respiratory support (invasive ventilation, bi-level positive airway pressure, or continuous positive airway pressure), and length of stay exceeding 72 h were used as measures of disease severity. Associations were investigated using multivariable logistic regression analyses. Multiple imputation was used to avoid bias and inference induced by missing data. Results: Risk factors associated with a need for respiratory support included age younger than 3 months of age [aOR: 6.73 (95% CI 2.71–16.7)], having siblings [aOR: 1.65 (95% CI 1.05–2.59)] and comorbidity [aOR: 2.40 (95% CI 1.35–4.24)]. The length of hospital stay >72 h was significantly associated with being younger than 3 months of age [aOR: 3.52 (95% CI 1.65–7.54)], having siblings [aOR: 1.45 (95% CI 1.01–2.08)], and comorbidity [aOR: 2.18 (95% CI 1.31–3.61)]. Sub-group analysis of children younger than 6 months of age confirmed the association between both young age and having siblings and the need for respiratory support. Conclusion: In a large cohort of children <59 months hospitalized with RSV infection, young age, comorbidity, and having siblings were associated with more severe disease.

• Pernica, Jeffrey M.; Arscott-Mills, Tonya; Steenhoff, Andrew P.; Mokomane, Margaret; Moorad, Banno & Bapabi, Mbabi [Show all 22 contributors for this article] (2022). Optimising the management of childhood acute diarrhoeal disease using a rapid test-and- treat strategy and/or Lactobacillus reuteri DSM 17938: A multicentre, randomised, controlled, factorial trial in Botswana. BMJ Global Health. 7:e007826(4), p. 1–12. doi: 10.1136/bmjgh-2021-007826. Full text in Research Archive Show summary

  Introduction The study aim was to determine if rapid enteric diagnostics followed by the provision of targeted antibiotic therapy (‘test-and-treat’) and/or Lactobacillus reuteri DSM 17938 would improve outcomes in children hospitalised in Botswana with acute gastroenteritis. Methods This was a multicentre, randomised, factorial, controlled, trial. Children aged 2–60 months admitted for acute non-bloody diarrhoea to four hospitals in southern Botswana were eligible. Participants were assigned to treatment groups by web-based block randomisation. Test-and-treat results were not blinded, but participants and research staff were blinded to L. reuteri/placebo assignment; this was dosed as 1×108 cfu/mL by mouth daily and continued for 60 days. The primary outcome was 60-day age-standardised height (HAZ) adjusted for baseline HAZ. All analyses were by intention to treat. The trial was registered at Clinicaltrials.gov. Results Recruitment began on 12 June 2016 and continued until 24 October 2018. There were 66 participants randomised to the test-and-treat plus L. reuteri group, 68 randomised to the test-and-treat plus placebo group, 69 to the standard care plus L. reuteri group and 69 to the standard care plus placebo group. There was no demonstrable impact of the test-and-treat intervention (mean increase of 0.01 SD, 95% CI −0.14 to 0.16 SD) or the L. reuteri intervention (mean decrease of 0.07 SD, 95% CI −0.22 to 0.08 SD) on adjusted HAZ at 60 days. Conclusions In children hospitalised for acute gastroenteritis in Botswana, neither a test-and-treat algorithm targeting enteropathogens, nor a 60-day course of L. reuteri DSM 17938, were found to markedly impact linear growth or other important outcomes. We cannot exclude the possibility that test-and-treat will improve the care of children with significant enteropathogens (such as Shigella) in their stool. Trial registration number NCT02803827.

• Lyamouri, Miriam; Mårild, Karl Staffan; Nielsen, Rasmus Gaardskær & Størdal, Ketil (2022). Proton pump inhibitors for infants in three Scandinavian countries increased from 2007 to 2020 despite international recommendations. Acta Paediatrica. ISSN 0803-5253. 111(11), p. 2222–2228. doi: 10.1111/apa.16491. Full text in Research Archive Show summary

  Aim There is weak evidence that proton pump inhibitors (PPIs) alleviate non-specific complaints often attributed to gastroesophageal reflux in infancy and international guidelines do not recommend their use. We studied PPIs dispensed for infants in three Nordic countries. Methods This was an observational population-based study of infants living in Norway, Sweden and Denmark in 2007–2020. We used nationwide pharmaceutical registers to study dispensed PPIs. The data provided a total of 3.3 million observed years on about 240 000 annual births. Results The overall use of PPIs in infancy showed a marked increase in all three countries from 2007 to 2020. In 2020, PPI dispensing was 46.4, 23.4 and 18.9 per 1000 per year in infants aged 0–11 months in Denmark, Norway and Sweden. These were increases of 357%, 585% and 556% respectively. Although the rate was highest in Denmark, it had decreased by 42% in the last 3 years of the study. Conclusion Despite international recommendations against routine PPI prescribing in infancy, dispensed PPIs increased more than fourfold on average in three Nordic countries from 2007 to 2020. The reason for this notable increase could not be established from the data, but the large variations over time, and between the countries, probably indicated unwarranted use.

• Ulnes, Maria; Albrektsson, Henrik; Størdal, Ketil; Saalman, Robert; Ludvigsson, Jonas F. & Mårild, Karl Staffan (2022). Regional Swedish study found that one in seven coeliac patients experienced loss of follow up during childhood. Acta Paediatrica. ISSN 0803-5253. p. 1–12. doi: 10.1111/apa.16633. Full text in Research Archive Show summary

  Aim To examine the clinical follow up of paediatric coeliac disease and the rate of loss of follow up during childhood, for which data are scarce. Methods In a cohort of coeliac children diagnosed in 2013–2018 in Gothenburg, Sweden, we retrospectively explored the follow-up practice of paediatric coeliac disease until June 2021. We used medical records from hospital-based paediatric gastroenterology and general paediatric outpatient clinics, laboratory records, and questionnaires. Loss of follow up was defined no coeliac disease-related follow up or tissue transglutaminase test over the past 2 years of study enrolment. Results We included 162 children (58% girls) aged 7.8–18.2 years (average 12.7). Most participants (76%) were followed at general paediatric outpatient clinics rather than hospital-based clinics. After 2.3–8.8 (average 5.3) years since diagnosis, 23 patients (14%; 95% confidence interval, 9%–21%) had been lost to follow up. Patients with loss of follow up were more often boys (61% versus 39%, p = 0.08), with a somewhat longer average disease duration of 5.8 versus 5.2 years (p = 0.11). There were no between-group differences in socio-economic characteristics and patient-reported experience measures of coeliac disease care. Conclusion One in seven coeliac patients may experience loss of follow up during childhood.

• Mearin, Maria Luisa; Agardh, Daniel; Antunes, Henedina; Al-Toma, Abdul; Auricchio, Renata & Castillejo, Gemma [Show all 34 contributors for this article] (2022). ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents with Celiac Disease. Journal of Pediatric Gastroenterology and Nutrition - JPGN. ISSN 0277-2116. 75(3), p. 369–386. doi: 10.1097/MPG.0000000000003540. Full text in Research Archive

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• Hestetun, Sigrid Valen; Haftorn, Kristine Løkås; Størdal, Ketil & Sanner, Helga (2025). Reply. Arthritis & Rheumatology. ISSN 2326-5191. 77(12), p. 1807–1808. doi: 10.1002/art.43239. Full text in Research Archive
• Øymar, Knut Asbjørn Alexander; Tjora, Erling & Størdal, Ketil (2025). Ammende trenger sjelden å slutte med kumelk. 145, p. 1–7. doi: 10.4045/tidsskr.25.0349. Full text in Research Archive Show summary

  Matallergi mistenkes ofte som årsak til symptomer hos barn i første leveår. Det er vanlig å anbefale at ammende mødre også slutter å innta enkelte matvarer. Det er ikke godt faglig begrunnet.

• Størdal, Ketil (2025). Hvor mye skal barna på Gaza tåle? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 145(8), p. 1–4. doi: 10.4045/tidsskr.25.0357. Full text in Research Archive
• Klingenberg, Claus Andreas; Norderval, Stig & Størdal, Ketil (2025). Hvorfor skrive cor, pulm og abdomen i år 2025? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 145(9). doi: 10.4045/tidsskr.25.0248. Full text in Research Archive
• Koletzko, Berthold; Dalt, Liviana da; De Guchtenaere, Ann; Dembinski, Lukasz; Grossman, Zachi & Hadjipanayis, Adamos [Show all 8 contributors for this article] (2024). European Academy of Paediatrics demands protection of children's rights endangered by the ongoing Israel Gaza conflict. Acta Paediatrica. ISSN 0803-5253. doi: 10.1111/apa.17400. Full text in Research Archive
• Fewtrell, Mary; Baumann, Ulrich; Bronsky, Jiri; Haiden, Nadja; Hill, Susan & Kivelä, Laura [Show all 60 contributors for this article] (2024). World Health Organization (WHO) guideline on the complementary feeding of infants and young children aged 6−23 months 2023: A multisociety response. Journal of Pediatric Gastroenterology and Nutrition - JPGN. ISSN 0277-2116. 79(1), p. 181–188. doi: 10.1002/jpn3.12248. Full text in Research Archive
• Heen, Espen Kolstad; Størdal, Ketil; Wachira, John; Heen, Ingjerd & Lundeby, Karen Marie (2023). Do we need a new global policy for ending preventable perinatal deaths in fragile low-income countries? Journal of Global Health. ISSN 2047-2978. 13. doi: 10.7189/jogh.13.03008. Full text in Research Archive
• Stocker, Martin; Klingenberg, Claus Andreas; Navér, Lars; Nordberg, Viveka; Berardi, Alberto & Helou, Salhab el [Show all 25 contributors for this article] (2023). Less is more: Antibiotics at the beginning of life. Nature Communications. 14(1). doi: 10.1038/s41467-023-38156-7. Full text in Research Archive Show summary

  Antibiotic exposure at the beginning of life can lead to increased antimicrobial resistance and perturbations of the developing microbiome. Early-life microbiome disruption increases the risks of developing chronic diseases later in life. Fear of missing evolving neonatal sepsis is the key driver for antibiotic overtreatment early in life. Bias (a systemic deviation towards overtreatment) and noise (a random scatter) affect the decision-making process. In this perspective, we advocate for a factual approach quantifying the burden of treatment in relation to the burden of disease balancing antimicrobial stewardship and effective sepsis management.

• Størdal, Ketil & Hjørleifsson, Stefan (2023). Fem år med Gjør kloke valg – hjelper det? 143(17). doi: 10.4045/tidsskr.23.0627. Full text in Research Archive
• Brun, Anne Charlotte; Størdal, Ketil; Kvammen, Janne Anita; Thomassen, Rut Anne & Henjum, Sigrun (2023). Ikke bare barnemat. Full text in Research Archive
• Midtsund, Astrid Durdei; Brun, Anne Charlotte; Størdal, Ketil; Kvammen, Janne Anita; Thomassen, Rut Anne & Brattlie, Marianne [Show all 7 contributors for this article] (2023). Ikke bare barnemat. Full text in Research Archive
• Kvammen, Janne Anita; Brattlie, Marianne; Thomassen, Rut Anne; Størdal, Ketil; Midtsund, Astrid Durdei & Brun, Anne Charlotte [Show all 7 contributors for this article] (2023). Ubegrunnet usikkerhet om spedbarnsmat. Full text in Research Archive
• Andersen, Svend; Bernklev, Tomm; Størdal, Ketil; Perminow, Gøri & Høivik, Marte Lie (2022). Paediatric IBD incidence increases in South-East Norway. Full text in Research Archive
• Havdal, Lise Beier; Bøås, Håkon; Bekkevold, Terese; Kran, Anne-Marte Bakken; Rojahn, Astrid & Størdal, Ketil [Show all 15 contributors for this article] (2022). Corrigendum to ‘The burden of respiratory syncytial virus in children under 5 years of age in Norway’ [Journal of Infection Volume 84, Issue 2 (2022) Pages 205-215, (S0163445321005995), (10.1016/j.jinf.2021.12.008)]. Journal of Infection. ISSN 0163-4453. doi: 10.1016/j.jinf.2022.12.018. Full text in Research Archive
• Rettedal, Siren; Kibsgaard-Petersen, Amalie; Eilevstjønn, Joar; Kvaløy, Jan Terje; Bjorland, Peder Aleksander & Lillevik, Hanne Markhus [Show all 12 contributors for this article] (2022). Impact of immediate and continuous heart rate feedback by dry electrode ECG on time to initiation of ventilation after birth: protocol for a randomised controlled trial. BMJ Open. 12(9), p. 1–6. doi: 10.1136/bmjopen-2022-061839. Full text in Research Archive Show summary

  Introduction 3%–8% of newborns need positive pressure ventilation (PPV) after birth. Heart rate (HR) is considered the most sensitive indicator of the newborns’ condition and response to resuscitative interventions. According to guidelines, HR should be assessed and PPV initiated within 60 s after birth in non-breathing newborns. Dry electrode ECG can provide accurate feedback on HR immediately after birth and continuously during resuscitation. The impact of early and continuous HR feedback is unknown. Method and analysis This single-centre randomised controlled trial seeks to determine if HR feedback by dry electrode ECG immediately after birth and continuously during newborn resuscitation results in more timely initiation of PPV, improved ventilation and short-term outcomes compared with standard HR assessment. In all newborns≥34 gestational weeks, the dry electrode ECG sensor is placed on the upper abdomen immediately after birth as an additional modality of HR assessment. The device records and stores HR signals. In intervention subjects, the HR display is visible to guide decision-making and further management, in control subjects the display is masked. Standard HR assessment is by stethoscope, gel-electrode ECG and/or pulse oximetry (PO). Time of birth is registered in the Liveborn app. Time of initiation and duration of PPV is calculated from video recordings. Ventilation parameters are retrieved from the ventilation monitor, oxygen saturation and HR from the PO and gel-electrode ECG monitors. The primary endpoint is proportion of resuscitated newborns who receive PPV within 60 s after birth. To detect a 50% increase with power of 90% using an overall significance level of 0.05 and 1 interim analysis, 169 newborns are needed in each group. Ethics and dissemination Approval by the Norwegian National Research Ethics Committee West (2018/338). Parental consent is sought at routine screening early in pregnancy. The results will be published in peer-reviewed journal and presented at conferences.

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