May-Bente Bengtson

Irritable bowel syndrome in twins: genes and environment

Background and aims: Both environmental and genetic factors may contribute to irritable bowel syndrome (IBS). Nutrition in fetal life, an early environmental factor, seems to influence the development of chronic diseases later in life, such as coronary heart disease, hypertension, and non-insulin diabetes. This population based twin study evaluated the association between intrauterine growth, measured by weight and gestational age, and IBS. Structural equation analyses were conducted to analyse genetic and environmental sources of variation in liability to IBS. Methods: A postal questionnaire was sent to 12 700 Norwegian twins born between 1967 and 1979. The questionnaire included a checklist of 31 illnesses and symptoms, including IBS. The influence of birth weight on developing IBS was tested in four weight groups. Disease discordant monozygotic (MZ) pairs were analysed to test the association between intrauterine growth and IBS. Results: Concordance for IBS was significantly greater (p = 0.011) in monozygotic (22.4%) than in dizygotic (9.1%) twins. The heritability of IBS was estimated to be 48.4% among females. Birth weight below 1500 g (adjusted odds ratio 2.4 (95% confidence interval 1.1, 5.3)) contributed significantly to the development of IBS, which appeared 7.7 years earlier than in higher weight groups. In the MZ group with birth weights lower than 2500 g, twins with IBS were significantly lighter than twins without disease (190.6 g; p = 0.02). Conclusion: The present study demonstrates that restricted fetal growth has a significant influence on the development of IBS later in life. Weight below 1500 g influences age at onset. Genetic contribution appears to be important for IBS among females.

Relationships between inflammatory bowel disease and perinatal factors: Both maternal and paternal disease are related to preterm birth of offspring

Background:The aims of this study were to explore the influences of familial, maternal, and paternal inflammatory disease (IBD) on perinatal outcomes in the offspring and the risk for development of IBD related to perinatal factors. Methods:Eighty‐five patients with Crohns disease (CD) and 86 with ulcerative colitis (UC) were included from a population‐based incidence study enrolled 1990–1994. Family and birth records of these patients, as well as of their 207 infants, were drawn from the Norwegian Medical Birth Registry, established in 1967, and compared with the national birth cohort from the same period. Results:Maternal (odds ratio [OR] = 2.15, 95% confidence interval [CI]: 1.36, 3.39) and paternal IBD (OR = 3.02, 95% CI: 1.82, 5.01) influenced the risk of preterm birth (<37 weeks), which further increased if the affected parents had a first‐degree relative with IBD (OR = 4.29, 95% CI: 1.59, 11.63). Maternal CD was associated with lower birth weight in the offspring (crude difference: 271.79 g, 95% CI: 87.83, 455.77, versus controls). Maternal UC increased the risk of perinatal bacterial infection in the offspring (OR = 6.03, 95% CI: 2.03, 17.91). IBD patients (2.3%) were less likely to be delivered by cesarean section than controls (8.1%) (OR = 0.27, CI: 95%: 0.10, 0.73). Conclusions:Familial, maternal, and paternal IBD were linked to preterm birth, which might be explained by genetic mechanisms. The present protective effect of cesarean sections needs further clarification in future studies. Inflamm Bowel Dis 2009

Geographic Distribution and Ecological Studies of Inflammatory Bowel Disease in Southeastern Norway in 1990-1993

Background: The purpose was to study the spatial distribution of cases of inflammatory bowel disease (IBD) and characterize municipalities with high incidences in a search for environmental risk factors. Methods: Spatial clustering of patients diagnosed with IBD during 1990–1993 were studied in 4 counties in southeastern Norway, and an ecological analysis was conducted to study the relationship between risk of IBD in the municipalities and their characteristics such as population, health care, urban/rural change, and socioeconomic change. Results: One cluster consisting of 4 municipalities was identified for IBD in ϕstfold county (P = 0.011). The ecological analysis showed that the incidence rate of IBD was 33% (95% confidence interval [CI]: 2%–75%) higher in municipalities with the highest level of education compared to the lowest level of education and 35% (2%–78%) higher in urban than rural municipalities. The incidence rate was 11% (1%–20%) lower in municipalities with a high urban/rural change compared to municipalities with low urban/rural change. Individuals living in high‐risk municipalities were 3 times (1.57–5.45) more likely to have a first‐degree family member with IBD than individuals living in normal‐risk municipalities. Conclusions: The geographic distribution of cases with IBD is not uniformly distributed and is related to urbanization, level of education, and moving pattern. Geographic distribution may be explained by either changes in environment–host relationships or neurobiological mechanisms due to stress and economic frustration. These factors and genetic predisposition might also explain increased familial clustering. Spatial clustering was significant neither for Crohns disease CD nor ulcerative colitis (UC) but showed a stronger tendency within the CD group.

Clustering in time of familial IBD separates ulcerative colitis from Crohn's disease

Background: The aim was to compare clustering of time at diagnosis and phenotype of inflammatory bowel disease (IBD) between affected parents and children and to explore generational differences in age at diagnosis (AAD) as well as the concordance of clinical characteristics. Methods: Eighty‐four affected pairs from 45 families were included from 5 counties in southeastern Norway between August 2003 and December 2006; 43 were sib‐sib pairs and 39 parent‐child pairs. Clinical data were obtained by phone interviews and by hospital records. Results: The difference in median AAD was 17.0 years (P < 0.001) and 2.0 years (P = 0.29) in parent‐child and sib‐sib pairs, respectively. When the time interval between diagnosis in parent and child was split into 2 groups, below and above 5 years, 64% of pairs with ulcerative colitis (UC) offspring were diagnosed within 5 years, compared to 24% of pairs with Crohns disease (CD) offspring (odds ratio [OR] = 5.7, 95% confidence interval [CI]: 1.4, 23.8). Concordance for smoking habits was low in 26 pairs with mixed disease (&kgr; = 0.15), whereas patients with CD tended to be current smokers. Conclusions: Most of the children acquire their disease at an earlier time in life compared to their parents, suggesting genetic anticipation. The time interval between diagnosis of the parents and offspring was lower when the offspring developed UC compared to CD, which might reflect the influence of shared environment on the generational difference in AAD in UC families. This study confirmed the effect of smoking habits on IBD phenotype. Inflamm Bowel Dis 2009

Familial aggregation in Crohn's disease and ulcerative colitis in a Norwegian population-based cohort followed for ten years

BACKGROUND AND AIMS To explore the change in risk among 1st degree relatives of ulcerative colitis (UC) and Crohns disease (CD) for development of concordant disease in an incidence cohort followed for ten years. Furthermore, we wanted to compare familial and sporadic cases regarding clinical characteristics and the course of the disease. METHODS This population-based study included 421 patients with UC and 197 with CD enrolled from 1990 to 1994. Clinical characteristics and the number of 1st degree relatives of the patients were recorded continuously during ten years. RESULTS Age at diagnosis in CD patients (OR=0.95, 95% CI: 0.93-0.98) and cumulative relapse rate in UC patients (OR=4.91, 95% CI=1.16, 20.75) were significantly associated to familial clustering. Based on the calculated population prevalence of CD (262/100000) and UC (505/100000), the age-adjusted risk for development of concordant disease was 25.9 and 8.6 among siblings and parents of CD, respectively. In UC, the corresponding risks were 8.6 and 1.5. In the course of ten years the increase in risk was observed only among siblings (28%) and parents (97%) of UC, in contrast to no increase in CD. Moreover, the concordance for UC was high in three generations. CONCLUSIONS Our study confirmed the importance of genetic influence on the development of CD. Within an observation period of ten years, the increased concordance and relapse rate in familial UC, might point to a larger genetic component in UC than previously suggested.

Concordance for IBD among twins compared to ordinary siblings--a Norwegian population-based study.

AIMS Comparing the risk to develop concordant disease among twins with inflammatory bowel disease (IBD) to ordinary siblings. Moreover, clinical characteristics of IBD and the association between perinatal factors and IBD, were evaluated. METHODS Patients with IBD, enrolled from an incidence study between 1990 and 1994, and the twins were identified from the Norwegian national birth registry, which was established in 1967. RESULTS Eight monozygotic and 16 dizygotic pairs, in which at least one twin reported a positive history of IBD were compared to 84 patients with Crohns disease (CD) and 87 patients with ulcerative colitis (UC) from the incidence study. The relative risks for concordant disease in monozygotic pairs were estimated to 95.4 (95% CI: 76.3, 114.6) and 49.5 (95% CI: 35.7, 63.3) for CD and UC, respectively. The corresponding risks in dizygotic pairs were 42.4 (95% CI: 29.6, 55.2) and 0.0. Among ordinary siblings of CD and UC the risks for concordance were 22.7 (95% CI: 13.3, 32.1) and 4.6 (95% CI: 0.4, 8.7), respectively. Stricturing disease was significantly higher in twins with CD compared to incidental cases. The first-born twin in pairs discordant for disease, 12 out of 19 (63.2%), tended to be affected by IBD (p=0.10). CONCLUSION Genetic factors influence the development of IBD and fibrostenotic disease in CD. The increased risk for concordant disease among dizygotic twins compared to ordinary siblings, at least in CD, might underscore the importance of shared environment in utero or in childhood.

Inadequate Gestational Weight Gain, the Hidden Link Between Maternal Ibd and Adverse Pregnancy Outcomes: Results from the Norwegian Mother and Child Cohort Study

Background: Patients with inflammatory bowel disease (IBD) are in general prone to weight loss. We explored the risk of inadequate gestational weight gain (GWG), and the impact of GWG on adverse pregnancy outcomes, among mothers with IBD in the Norwegian Mother and Child Cohort Study (MoBa). Methods: The MoBa with 95,200 mothers enrolled from 1999 to 2008, comprised 217 mothers with ulcerative colitis and 166 with Crohns disease. Demographics were ascertained through a basic questionnaire before the first ultrasound visit and an IBD history and disease activity during pregnancy through a questionnaire mailed out in 2013. Inadequate GWG was based on the US Institute of Medicine recommendations. The associations between IBD and inadequate GWG or adverse pregnancy outcomes were explored, adjusted for diabetes, hypertension, smoking, maternal age, education, and disease activity. Results: Mothers with Crohns disease (34.3%) and ulcerative colitis (26.7%) were more frequently exposed to inadequate GWG compared with non-IBD mothers (19.4%) (adjusted odds ratio [aOR] = 2.02, 95% confidence interval [CI], 1.42–2.86 and aOR = 1.46, 95% CI, 1.04–2.05, respectively). Mothers with IBD with inadequate GWG (exposed) had a 2-fold risk of small for gestational age infants compared with exposed non-IBD mothers (aOR = 1.93, 95% CI, 1.13–3.29). Exposed mothers with Crohns disease and ulcerative colitis had a several-fold increased risk of small for gestational age compared with nonexposed IBD mothers (aOR = 4.5, 95% CI, 1.3–16.2, aOR = 5.5, 95% CI, 1.6–18.5). Disease activity was associated with reduced GWG (<13 kg compared with >17.5 kg) (aOR = 3.34, 95% CI, 1.33–8.38). Conclusions: Inadequate GWG should be considered as a risk factor for adverse pregnancy outcomes or as a marker of disease activity.

Can temperature explain the latitudinal gradient of ulcerative colitis? Cohort of Norway

BackgroundIncidence and prevalence of ulcerative colitis follow a north–south (latitudinal) gradient and increases northwards at the northern hemisphere or southwards at the southern hemisphere. The disease has increased during the last decades. The temporal trend has been explained by the hygiene hypothesis, but few parallel explanations exist for the spatial variability. Many factors are linked to latitude such as climate. Our purpose was to investigate the association between variables governing the climate and prospectively identified patients.MethodsIn this study, we used a subset of the population-based Cohort of Norway (n = 80412) where 370 prevalent cases of ulcerative colitis were identified through self-reported medication. The meteorological and climatic variables temperature, precipitation, and altitude were recorded from weather stations of the Norwegian Meteorological Institute. Summer temperature was used to capture environmental temperature.ResultsSummer temperature was significantly related to the prevalence of ulcerative colitis. For each one-degree increase in temperature the odds for ulcerative colitis decreased with about 9% (95% CI: 3%-15%). None of the other climatic factors were significantly associated to the risk of ulcerative colitis. Contextual variables did not change the association to the prevalence of ulcerative colitis.ConclusionsThe present results show that the prevalence of ulcerative colitis is associated to summer temperature. Our speculation is that summer temperature works as an instrumental variable for the effect of microbial species richness on the development of ulcerative colitis. Environmental temperature is one of the main forces governing microbial species richness and the microbial composition of the commensal gut flora is known to be an important part in the process leading to ulcerative colitis.

Ankylosing Spondylitis and Axial Spondyloarthritis in Patients With Long-term Inflammatory Bowel Disease: Results From 20 Years of Follow-up in the IBSEN Study

Background Patients with inflammatory bowel disease [IBD] often suffer from rheumatic manifestations, including inflammatory back disorders. The prevalence of these disorders late in the course of IBD is poorly investigated. The aim of this study was to estimate the prevalence of inflammatory back disorders in patients with IBD 20 years after diagnosis, and to investigate possible associations with IBD severity, HLA-B27, and the NOD2 genotype. Methods A population-based cohort [the IBSEN study] was followed prospectively for 20 years. Information covering IBD activity and rheumatic diseases was collected at the regular follow-ups. HLA-B27 and NOD2 were analysed as present or absent. Results At 20 years, 599 members of the original cohort were alive, of whom 470 [78.5%] were investigated [314 ulcerative colitis and 156 Crohns disease patients]. Ankylosing spondylitis was diagnosed in 21 patients [4.5%], axial spondyloarthritis was diagnosed in 36 patients [7.7%], and inflammatory back pain was diagnosed in 54 patients [11.5%]. Chronic back pain [back pain > 3 months] was present in 220 patients [46.8%]. HLA-B27 was associated with ankylosing spondylitis, axial spondyloarthritis, and inflammatory back pain, whereas no significant association was found for NOD2. A more chronic IBD course was associated with axial spondyloarthritis. Conclusions Our data revealed a high prevalence of ankylosing spondylitis, axial spondyloarthritis, and inflammatory back pain 20 years after the IBD diagnosis. HLA-B27 but not NOD-2 was a predisposing factor for the inflammatory back disorders in IBD patients. Axial spondyloarthritis was associated with a more chronic active IBD disease course.

Social Support and Strain Across Close Relationships: A Twin Study

Social relationships play a critical role in health and well-being throughout life. We analyzed the genetic and environmental variance co-variance structure for social support and strain across four sets of relationships including with one’s co-twin, spouse/partner, family and friends. The sample included 5288 Norwegian twins aged 40–80. Older people reported less support from their co-twin and friends and less strain from their family and friends. Genetic influences contribute importantly to variation across all the measures, with estimates ranging from 0 to 58%; variance due to shared environmental influences was most important for the twin-relationship, ranging from 0.11 to 0.42%. Social support was negatively correlated with social strain across all sets of relationships. With the exception of the co-twin relationship, these associations were primarily mediated by genetic and non-shared environmental effects.