Umeå University's logo

Background: Non-communicable diseases (NCDs) are a global health issue, posing a substantial burden on the individual, community, and public health. The risk of developing NCDs is influenced by a complex interplay between genetic, epigenetic, and environmental factors.

Methods: The NorthPop Birth Cohort Study (NorthPop) constitutes an infrastructure enabling cutting-edge research on the foundational pathways to NCDs in childhood, including allergic diseases and asthma, overweight/obesity, cognitive and neurodevelopmental dysfunction, gastrointestinal disorders, and caries. NorthPop aims at recruiting 10,000 families. Pregnant women and their partners residing in Västerbotten County, Sweden are eligible. Recruitment started in 2016 and is anticipated to end in 2025. Extensive data on parental, fetal and child health outcomes, lifestyle, diet, and environmental exposures are prospectively collected using web-based questionnaires in pregnancy and childhood until the children turn 7 years old. Urine samples are collected from the pregnant woman at gestational age 14–24 weeks. Blood samples are collected at gestational age 28 weeks. Placenta and cord blood are collected at birth. A breast milk sample is collected 1 month postpartum. Blood samples from the children are collected at 18 months and 7 years of age. Oral swabs and fecal samples are collected from the children within 48 h of birth, at 1, 9 and 18 months, 3 and 7 years of age. At age 7 years, children are invited to a follow-up visit, including measurements of weight, height, blood pressure, pulse, hand grip strength, working memory, skin prick test and saliva sampling. Additional measurements, such as sleep–wake and light exposure, and additional biological samples are collected in sub-cohorts. Permission for linkage to medical records and national registers e.g., the Swedish Pregnancy Register, the National Patient Register, the Longitudinal Integration Database for Health insurance and Labor market studies and the Swedish Prescribed Drug Register has been granted.

Discussion: Our multidisciplinary approach allows us to study how early life exposures, as well as parental health and lifestyle, influence future health in the offspring. Our results are anticipated to contribute to the understanding of disease risk and may inform future strategies aimed at risk reduction, highly significant for public health.

Trial registration: Retrospectively registered at Researchweb 11 November 2024 (project number 279272).

Aim: We evaluated the effect on body mass index standard deviation score (BMI-SDS) of a combined treatment (Web-COP) for children with obesity, including a web-based component targeting their parents.

Methods: This randomised controlled trial recruited children 5–12 years of age with obesity (International Obesity Task Force BMI [IOTF-BMI] ≥30 kg/m2) from school health care and outpatient paediatric clinics in in Northern Sweden from 1 June 2019 to 21 June 2020. The children were randomised to Web-COP, an intervention with group sessions and a 12-week web-based component, or standard care. The primary outcome was the change in IOTF BMI-SDS after 6 months.

Results: In total, 75 children (33 girls), mean age 9.5 years, were randomised, and 65/75 (87%) children and their parents completed the study, 35/39 (90%) in the Web-COP intervention and 30/36 (83%) in the standard care group. BMI-SDS at 6 months was changed from 3.08 to 2.81 in the intervention group compared to an increase from 3.07 to 3.16 in the standard care group, representing a significant difference between groups (p < 0.001). In the intervention group, 14/30 (47%) reduced their BMI-SDS ≥0.25, compared to none in the standard care group.

Conclusion: The parent-focused intervention significantly improved BMI-SDS in children with obesity as compared to children in standard care.

OBJECTIVE: We previously performed a population-based mass screening of coeliac disease in children aged 12 years in two birth cohorts resulting in 296 seropositive children, of whom 242 were diagnosed with coeliac disease after duodenal biopsies. In this follow-up study, we wanted to identify new cases in the screening population that tested negative-either converting from potential coeliac disease (seropositive but normal duodenal mucosa) or converting from seronegative at screening to diagnosed coeliac disease.

METHODS: All seropositive children were invited to a follow-up appointment 5 years after the screening with renewed serological testing and recommended endoscopic investigation if seropositive. Seronegative children in the screening study (n=12 353) were linked to the National Swedish Childhood Coeliac Disease Register to find cases diagnosed in healthcare during the same period.

RESULTS: In total, 230 (77%) came to the follow-up appointment, including 34 of 39 with potential coeliac disease. Of these, 11 (32%) had converted to coeliac disease. One new case was found in the National Swedish Childhood Coeliac Disease Register who received the diagnosis through routine screening in children with type 1 diabetes.

CONCLUSIONS: There is a high risk of conversion to coeliac disease among those with potential disease. However, a negative screening test was associated with a very low risk for a clinical diagnosis within a follow-up period of 5 years.

Purpose: The Swedish National Patient Register (NPR) is often used in observational studies of childhood-onset inflammatory bowel disease (IBD) (<18 years of age) and its subtypes, but the validity of previously used register-based algorithms for capturing childhood-onset IBD has never been examined.

Methods: We identified a random sample of 233 individuals with at least two first ever diagnostic listings of IBD in the NPR between 2002 and 2014. We calculated the test characteristics for different register-based definitions of IBD and its subtypes using the Copenhagen criteria and the revised Porto criteria as gold standard, both based on medical chart review. We made assumptions of the occurrence of undiagnosed IBD in the general child population based on available literature.

Results: Out of 233 individuals with at least two diagnostic listings of IBD, 216 had true IBD, resulting in a positive predictive value (PPV) = 93% (95% confidence interval (CI) 89–96), sensitivity = 88% (95% CI 83–92), specificity = 100% (95% CI 100–100), and negative predictive value (NPV) = 100% (95% CI 100–100). The PPV for the NPR-based definitions of IBD subtypes at time of first IBD diagnosis and at end of follow-up were 78% (95% CI 69–86) and 88% (95% CI 80–94), respectively, for Crohn’s disease and 74% (95% CI 63–83) and 71% (95% CI 60–80), respectively, for ulcerative colitis.

Conclusion: The validity of register-based definitions of childhood-onset IBD in the Swedish NPR is high and can be used to identify patients in observational research.

Background: Living with undiagnosed symptomatic coeliac disease is connected with deteriorated health, and persons with coeliac disease often wait a long time for their diagnosis. A mass screening would lower the delay, but its cost-effectiveness is still unclear. Our aim was to determine the cost-effectiveness of a coeliac disease mass screening at 12 years of age, taking a life course perspective on future benefits and drawbacks.

Methods: The cost-effectiveness was derived as cost per quality-adjusted life-year (QALY) using a Markov model. As a basis for our assumptions, we mainly used information from the Exploring the Iceberg of Celiacs in Sweden (ETICS) study, a school-based screening conducted in 2005/2006 and 2009/2010, where 13,279 12-year-old children participated and 240 were diagnosed with coeliac disease, and a study involving members of the Swedish Coeliac Association with 1031 adult participants.

Results: The cost for coeliac disease screening was 40,105 Euro per gained QALY. Sensitivity analyses support screening based on high compliance to a gluten-free diet, rapid progression from symptom-free coeliac disease to coeliac disease with symptoms, long delay from celiac disease with symptoms to diagnosis, and a low QALY score for undiagnosed coeliac disease cases.

Conclusions: A coeliac disease mass screening is cost-effective based on the commonly used threshold of 50,000 Euro per gained QALY. However, this is based on many assumptions, especially regarding the natural history of coeliac disease and the effects on long-term health for individuals with coeliac disease still eating gluten.

Aim: In 2012, revised criteria for diagnosing childhood coeliac disease were published by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition and incorporated into the revised Swedish guidelines the same year. These made it possible, in certain cases, to diagnose coeliac disease without taking small bowel biopsies. This survey assessed the extent to which the new guidelines were implemented by Swedish paediatric clinics two years after their introduction.

Methods: In October 2014, we distributed a paper questionnaire including five questions on diagnostic routines to the 40 paediatric clinics in university or regional hospitals in Sweden that perform small bowel biopsies.

Results: All 36 (90%) clinics that responded used anti-tissue transglutaminase antibodies as the initial diagnostic test and some also used serological markers. Most clinics (81%) used endoscopy and took multiple duodenal biopsies, whereas only a few (19%) occasionally employed a suction capsule. Almost all clinics (86%) omitted taking small bowel biopsies in symptomatic children with repeatedly high coeliac serology and positive genotyping, thereby avoiding the need for invasive endoscopy under anaesthesia.

Conclusion: The 2012 Swedish Paediatric Coeliac Disease Diagnostic Guidelines had been widely accepted and implemented in routine health care two years after their introduction.

BACKGROUND & AIMS: Celiac disease is a chronic inflammatory disease of the small intestine mucosa due to permanent intolerance to dietary gluten. The aim was to elucidate the role of small intestinal epithelial cells in the immunopathology of celiac disease in particular the influence of celiac disease-associated bacteria.

METHODS: Duodenal biopsies were collected from children with active celiac disease, treated celiac disease, and clinical controls. Intestinal epithelial cells were purified and analyzed for gene expression changes at the mRNA and protein levels. Two in vitro models for human intestinal epithelium, small intestinal enteroids and polarized tight monolayers, were utilized to assess how interferon-γ, interleukin-17A, celiac disease-associated bacteria and gluten influence intestinal epithelial cells.

RESULTS: More than 25 defense-related genes, including IRF1, SPINK4, ITLN1, OAS2, CIITA, HLA-DMB, HLA-DOB, PSMB9, TAP1, BTN3A1, and CX3CL1, were significantly upregulated in intestinal epithelial cells at active celiac disease. Of these genes, 70% were upregulated by interferon-γ via the IRF1 pathway. Most interestingly, IRF1 was also upregulated by celiac disease-associated bacteria. The NLRP6/8 inflammasome yielding CASP1 and biologically active interleukin-18, which induces interferon-γ in intraepithelial lymphocytes, was expressed in intestinal epithelial cells.

CONCLUSION: A key factor in the epithelial reaction in celiac disease appears to be over-expression of IRF1 that could be inherent and/or due to presence of undesirable microbes that act directly on IRF1. Dual activation of IRF1 and IRF1-regulated genes, both directly and via the interleukin-18 dependent inflammasome would drastically enhance the inflammatory response and lead to the pathological situation seen in active celiac disease.

Background: Celiac disease (CD) is increasing worldwide, which might be due to the changing environmental and lifestyle exposures. We aimed to explore how conditions related to maternity, delivery and the neonatal period influence CD onset during childhood.

Methods: Using Sweden’s national registers we had access to information on 1 912 204 children born between 1991 and 2009, 6 596 of whom developed CD before 15 years of age. Logistic regression analyses were performed to determine how CD is associated with maternity, delivery and the neonatal period.

Results: Regardless of sex, a reduction in CD risk was observed in children born to mothers aged ≥35 years (odds ratio [OR] 0.8; 95 % confidence interval [CI] 0.7–0.9) and with high maternal income (OR 0.9; 95 % CI 0.8–0.9). Being a second-born child, however, was positively associated with CD. Among boys, elective caesarean delivery increased the risk of CD (OR 1.2; 95 % CI 1.0–1.4), while maternal overweight (OR 0.9; 95 % CI 0.8-0.9), premature rupture of the membrane (OR 0.4; 95 % CI 0.2–0.8) and low birth weight showed a negative association. Girls had an increased CD risk compared to boys and in girls the risk was increased by repeated maternal urinary tract infections (OR 1.1; 95 % CI 1.0–1.2).

Conclusions: Elective caesarean delivery and repeated maternal urinary tract infections during pregnancy are associated with increased risk of CD onset during childhood, suggesting the role of dysbiosis during early life. High maternal age and high income reduced the risk of CD, which might be due to infant-feeding practices and life style.