Search

Stine Dydensborg Sander,1,2 Anne Vinkel Hansen,3,4 Ketil Størdal,5,6 Anne-Marie Nybo Andersen,3 Joseph A Murray,7 Steffen Husby1,2 1Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, Denmark; 2Institute of Clinical Research, Faculty of Health Science, University of Southern Denmark, Odense, Denmark; 3Department of Public Health, University of Copenhagen, Copenhagen, Denmark; 4Statistics Denmark, Copenhagen, Denmark; 5Department of Child Health, Norwegian Institute of Public Health, Oslo, Norway; 6Department of Pediatrics, Ostfold Hospital Trust, Grålum, Norway; 7Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA Purpose: The purpose of this study was to investigate the association between mode of delivery and the risk of celiac disease in two large population-based birth cohorts with different prevalence of diagnosed celiac disease. Patients and methods: This is an observational register-based cohort study using two independent population cohorts. We used data from administrative registers and health administrative registers from Denmark and Norway and linked the data at the individual level. We included all children who were born in Denmark from January 1, 1995 to December 31, 2010 and all children who were born in Norway from January 1, 2004 to December 31, 2012. Results: We included 1,051,028 children from Denmark. Cesarean sections were registered for 196,512 children (18.9%). Diagnosed celiac disease was registered for 1,395 children (0.13%). We included 537,457 children from Norway. Cesarean sections were registered for 90,128 children (16.8%). Diagnosed celiac disease was registered for 1,919 children (0.35%). We found no association between the mode of delivery and the risk of diagnosed celiac disease. The adjusted odds ratio for celiac disease for children delivered by any type of cesarean section compared to vaginal delivery was 1.11 (95% CI: 0.96–1.29) in the Danish cohort and 0.96 (95% CI: 0.84–1.09) in the Norwegian cohort. The adjusted odds ratio for celiac disease for children delivered by elective cesarean section compared to vaginal delivery was 1.20 (95% CI: 1.00–1.43) in the Danish cohort and 0.96 (95% CI: 0.79–1.17) in the Norwegian cohort. Conclusion: In this large registry-based study, mode of delivery was not associated with an increased risk of diagnosed celiac disease. Keywords: cesarean section, autoimmunity, epidemiology, administrative health register

Stine Dydensborg Sander,1-3 Ketil Størdal,4,5 Tine Plato Hansen,6 Anne-Marie Nybo Andersen,7 Joseph A Murray,8 Søren Thue Lillevang,9 Steffen Husby1,2 1Hans Christian Andersen Children’s Hospital, Odense University Hospital, 2Institute of Clinical Research, University of Southern Denmark, 3Odense Patient Data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark; 4Mental and Physical Health, Norwegian Institute of Public Health, Oslo, 5Department of Pediatrics, Ostfold Hospital Trust, Fredrikstad, Norway; 6Department of Pathology, Hvidovre Hospital, 7Department of Public Health, University of Copenhagen, Copenhagen, Denmark; 8Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; 9Department of Clinical Immunology, Odense University Hospital, Odense, Denmark Purpose: The purpose of this study was to validate the celiac disease diagnoses recorded in the Danish National Patient Register. To validate the diagnoses, we used information on duodenal biopsies from a national register of pathology reports (the Patobank) and information on celiac disease-specific antibodies and human leukocyte antigen (HLA) genotypes obtained from patient medical records.Patients and methods: We included all the children who were born from 1995 to 2012 and who were registered as having celiac disease in the Danish National Patient Register. We reviewed all the pathology reports on duodenal biopsies in the Patobank and the information in the medical records on celiac disease-specific antibodies (ie, anti-tissue transglutaminase 2 IgA and IgG, endomysial antibodies IgA, and anti-deamidated gliadin peptide IgG) and HLA genotypes.Results: We identified 2,247 children who were registered in the Danish National Patient Register with celiac disease. Duodenal biopsies for 1,555 of the children (69%) were registered in the Patobank; 1,127 (50%) had a biopsy that was compatible with celiac disease (ie, Marsh 2–3). We accessed the medical records of 95% of the children who were registered in the ­Danish National Patient Register with celiac disease. We found that 1,510 (67%) had one or more positive antibody-test results; 1,120 (50%) had anti-tissue transglutaminase 2, IgA at tenfold or greater the upper limit of the normal range and/or positive endomysial antibody results. The positive predictive value depended on the criteria used for validation and the types and numbers of registrations that were included in the analysis and ranged from 62% (95% confidence interval: 60%–64%) to 86% (95% confidence interval: 84%–87%).Conclusion: Our findings indicate that the Danish National Patient Register is a valuable source to identify patients who have been diagnosed with celiac disease. However, validation of the diagnoses is warranted before data on the patients are used for research purposes. Keywords: administrative health register, national patient register, pathology register, medical record, histology, serology

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 (≥90 th percentile, P90) vs low (

In recent years, wheat- and gluten-free diets have increased in demand due to reported increases in various conditions reported to be driven by ingredients of these food products. Celiac disease, wheat allergy and non-celiac wheat sensitivity constitute the three main categories of wheat-related disorders. Celiac disease is a well-characterized immune-mediated disease caused by immune reaction against specific gliadin epitopes, the main protein in wheat. Screening studies of samples collected over time bring evidence that there is a true increase in prevalence not only driven by increased testing activity. Clinical presentation of CeD is diverse and there is an increased risk of autoimmune co-morbidities. Wheat allergy consists of IgE- and non-IgE-mediated reactions, driven by Th2-cells directing eosinophil and basophil responses. Rapid IgE-mediated reactions are characterized by specific IgE antibodies in conjunction with symptoms originating especially from the respiratory and gastrointestinal tract. There is an increased risk of other allergies and the majority recover during adolescence. Non-IgE-mediated wheat allergy is a less-well defined condition, which is often diagnostically challenging due to a longer interval between exposure and symptoms and lack of non-invasive biomarkers. In this condition, wheat as a trigger needs to be established by exclusion followed by dietary challenge. Non-celiac wheat sensitivity, despite being the most recently recognized, has the highest reported prevalence among the three wheat-related entities. It remains, however, particularly poorly characterized due to unclear pathophysiology and lack of diagnostic markers. This narrative review will scrutinize the shared and distinct clinical features of the three wheat-related conditions, focusing on epidemiology, clinical presentation, co-morbidities, diagnosis, treatment and prognosis., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

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., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

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., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Conflict of interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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, I 2  = 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., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: We aimed to study the prevalence of hpyothermia 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., (© 2024 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

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., (© 2024 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

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 ., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2024 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

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., (© 2024 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

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., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

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., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

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., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

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., 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., 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., 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., Impact: In a study of 757,979 infants born in high-income countries, we report a presumed culture-negative early-onset sepsis incidence of 10.6/1000 livebirths with an associated antibiotic exposure of 77 antibiotic days per 1000 livebirths. This study sheds light on the major contribution of presumed culture-negative early-onset sepsis to early-life antibiotic exposure. Given the diagnostic uncertainty surrounding culture-negative early-onset sepsis, the low mortality rate, and the disproportionate antibiotic exposure associated with this condition, our study emphasizes the importance of targeting culture-negative early-onset sepsis in antimicrobial stewardship programs., Competing Interests: Competing interests: Alberto Berardi reported receiving personal fees from Atheneum Partners, GmbH outside the submitted work. Joseph M. Bliss reported receiving personal fees from Mead Johnson Nutrition outside the submitted work. No other disclosures were reported., (© 2024. The Author(s).)

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., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

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., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

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., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. KM: Birgitta och Göran Karlssons Stiftelse: Swedish Society for Medical Research, The Swedish Research Council, and ALF funding. ABIS was supported by Barndiabetesfonden (Swedish Child Diabetes Foundation); Swedish Council for Working Life and Social Research, Grant/Award Numbers: FAS2004-1775, FAS2004–1775; Swedish Research Council, Grant/Award Numbers: K2005-72X-11242-11A and K2008-69X-20826-01-4, K2008-69X-20826-01-4; Östgöta Brandstodsbolag; Medical Research Council of Southeast Sweden (FORSS); JDRF Wallenberg Foundation, Grant/Award Number: K 98-99D-12813-01A; ALF-and LFoU grants from Region Östergötland and Linköping university, Sweden; Joanna Cocozza Foundation. The funders had no role in study design, data collection, analysis, drafting of the manuscript or publication process., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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, p trend  <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., (© 2024 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

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 offspring should not be prioritised., (© 2024. The Author(s).)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have no competing interests to declare.

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., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Elmira Flem is currently employed by Merck & Co., Inc., North Wales, PA, USA. The work for the current study was conducted by Dr. Flem under the previous affiliation at the Norwegian Institute of Public Health. All other authors hereby declare that no other conflicts of interest exist., (Copyright: © 2024 Bøås et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Delayed hypersensitivity to gluten and milk protein is frequently reported but may be difficult to diagnose., Objective: We aimed to explore if a method of home-based double-blind placebo-controlled food challenges (H-FC) can identify and reduce unnecessary elimination diets in children., Methods: We included 73 of 92 children aged 1 to 17 years referred to a tertiary allergy clinic from 2011 to 2021 due to self-reported, delayed symptoms to gluten or milk. The children were randomized to H-FC, receiving gluten/milk protein or placebo for 5 to 7 days in a double-blind crossover manner, separated by 3 washout weeks. Patients/parents recorded symptoms using standardized forms. Two crossover periods were used from 2011 to 2016 and 3 periods from 2017 to 2021. A positive challenge required significantly more symptoms during the active period versus the placebo period. After the challenge, reintroduction of milk/gluten was assessed by a follow-up interview. The primary outcome was the proportion of children with a positive challenge., Results: The children, with a mean age of 11 years, had followed a strict gluten-free or milk-protein-free diet for a median duration of 24 months (range: 3-180 months). A positive challenge was observed in 18 of 73 children (25%), more often using 2 (35%) compared with 3 challenge periods (12%). At follow-up, 44 of 55 (80%) children with a negative challenge had successfully reintroduced milk/gluten., Conclusions: H-FC may be an effective method in avoiding unnecessary elimination diets in children. Only 25% of the challenges were positive, and 80% of the children with negative challenges succeeded in reintroducing the food. Three challenge periods may be necessary to reduce false-positive outcomes., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)