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.
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.
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.
In prospectively collected data from 3 population-based birth cohorts, the duration of exclusive or any breastfeeding was not associated with offspring IBD risk.
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Studies in mice suggest that early life represents a critical time window, where antibiotics may exert profound and lasting effects on the gut microbiota and metabolism. We aimed to test the ...hypothesis that prenatal antibiotic exposure is associated with increased risk of childhood overweight in a population-based cohort study. We linked 43,365 mother-child dyads from a nationwide cohort of pregnant women and their offspring to the Danish National Prescription Registry. Linear and logistic regression models were used to examine associations between prenatal exposure to antibiotics and BMI z-score and overweight (including obesity) at age seven and 11 years. Prenatal antibiotic exposure and childhood overweight were both associated with high pre-pregnancy BMI, maternal diabetes, multi-parity, smoking, low socioeconomic status, high paternal BMI, and short duration of breastfeeding. After adjustment for confounders, no associations were observed between prenatal antibiotic exposure and odds of overweight at age seven and 11 years. Whereas no association was observed between broad-spectrum antibiotics and overweight at age 11 years, exposure to broad-spectrum antibiotics was associated with higher odds of overweight at age seven years with an odds ratio of 1.27 (95% CI, 1.05-1.53) for ampicillin and an odds ratio of 1.56 (95% CI, 1.23-1.97) for amoxicillin. As we did not account for underlying infections, the observed associations with early childhood overweight could be explained by confounding by indication. In conclusion, our population-based study suggests that prenatal exposure to narrow-spectrum antibiotics is not associated with overweight in offspring. Exposure to some broad-spectrum antibiotics may increase the odds of overweight in early childhood, but the association does not persist in later childhood.
There is growing interest in the prediagnostic phase of inflammatory bowel disease (IBD) and in the overlap of IBD with other diseases. We described and compared use of any prescription medication ...between individuals with and without IBD in a 10-year period preceding diagnosis.
Based on cross-linked nationwide registers, we identified 29,219 individuals diagnosed with IBD in Denmark between 2005 and 2018 and matched to 292,190 IBD-free individuals. The primary outcome was use of any prescription medication in years 1-10 before IBD diagnosis/matching date. Participants were considered as medication users if they redeemed ≥1 prescription for any medication in the World Health Organization Anatomical Therapeutic Chemical (ATC) main groups or subgroups before diagnosis/matching.
The IBD population had a universally increased use of medications compared with the matched population before IBD diagnosis. At 10 years before diagnosis, the proportion of users was 1.1-fold to 1.8-fold higher in the IBD population in 12 of 14 ATC main groups of medication ( P -value < 0.0001). This applied across age, sex, and IBD subtypes, although it was the most pronounced for Crohn's disease (CD). Two years before diagnosis, the IBD population had a steep increase in medication use for several organ systems. When analyzing therapeutic subgroups of medication, the CD population exhibited 2.7, 2.3, 1.9, and 1.9 times more users of immunosuppressants, antianemic preparations, analgesics, and psycholeptics, respectively, than the matched population 10 years before diagnosis ( P -value < 0.0001).
Our findings demonstrate universally increased medication use years before IBD, especially CD, diagnosis and indicates multiorgan involvement in IBD.
To explore the natural microbial community of any ecosystems by high-resolution molecular approaches including next generation sequencing, it is extremely important to develop a sensitive and ...reproducible DNA extraction method that facilitate isolation of microbial DNA of sufficient purity and quantity from culturable and uncultured microbial species living in that environment. Proper lysis of heterogeneous community microbial cells without damaging their genomes is a major challenge. In this study, we have developed an improved method for extraction of community DNA from different environmental and human origin samples. We introduced a combination of physical, chemical and mechanical lysis methods for proper lysis of microbial inhabitants. The community microbial DNA was precipitated by using salt and organic solvent. Both the quality and quantity of isolated DNA was compared with the existing methodologies and the supremacy of our method was confirmed. Maximum recovery of genomic DNA in the absence of substantial amount of impurities made the method convenient for nucleic acid extraction. The nucleic acids obtained using this method are suitable for different downstream applications. This improved method has been named as the THSTI method to depict the Institute where the method was developed.
Abstract
Background and Aims
Patients with inflammatory bowel disease have increased risks of cardiovascular diseases, but the role of traditional and non-traditional cardiovascular risk factors ...remains unclear. We investigated if the cardiovascular risk profile differs between patients with inflammatory bowel disease and individuals in the general population.
Methods
We included a population of 108789 participants from the Copenhagen General Population Study of individuals of Danish descent aged 20–100 years. The population included 1203 individuals with prevalent inflammatory bowel disease 347 with Crohn’s disease and 856 with ulcerative colitis. The cardiovascular risk profile was assessed by traditional risk factors plasma lipids and glucose, body composition measures, and blood pressure and non-traditional risk factors inflammatory markers and biomarkers of liver and pancreas function.
Results
Even though patients with inflammatory bowel disease more frequently are diagnosed with cardiovascular diseases, traditional cardiovascular risk factors were not increased. Indeed, patients with inflammatory bowel disease had slightly lower plasma levels of total cholesterol and low-density lipoprotein cholesterol. Levels of inflammatory markers, particularly high-sensitivity C-reactive protein, were higher in individuals with versus without a diagnosis of inflammatory bowel disease, when assessed at a random point in time during the disease course.
Conclusions
The increased risk of cardiovascular diseases in patients with inflammatory bowel disease may be linked to chronic systemic inflammation rather than to traditional cardiovascular risk factors. Further studies need to examine whether cardiovascular-preventive strategies should focus on optimising management of inflammation in patients with inflammatory bowel disease rather than focusing on traditional cardiovascular risk factors.
We examined whether plasma C-reactive protein (CRP) levels at the time of diagnosis of breast cancer are associated with overall survival, disease-free survival, death from breast cancer, and ...recurrence of breast cancer.
We observed 2,910 women for up to seven years after they were diagnosed with invasive breast cancer (median follow-up time was three years). Plasma levels of high-sensitivity CRP were measured at the time of diagnosis and we assessed the association between CRP levels and risk of reduced overall and disease-free survival, death from breast cancer, and recurrence of breast cancer by using the Kaplan-Meier method and Cox proportional hazards regression. During follow-up, 383 women died (225 of whom died from breast cancer) and 118 women experienced recurrence of breast cancer.
Elevated CRP levels across tertiles at the time of diagnosis were associated with reduced overall and disease-free survival and with increased risk of death from breast cancer (log-rank trend for all, P < 0.001), but not with recurrence. The multifactor-adjusted hazard ratios (HR) of reduced overall survival among women in the middle and highest versus the lowest tertile of CRP were 1.30 (95% CI, 0.97 to 1.73) and 1.94 (1.48 to 2.55), respectively. Corresponding HRs of reduced disease-free survival were 1.16 (0.89 to 1.50) and 1.76 (1.38 to 2.25) and of death from breast cancer 1.22 (0.84 to 1.78) and 1.66 (1.15 to 2.41). Dividing CRP levels into octiles resulted in a stepwise increased risk of reduced overall survival (P for trend <0.001) and the multifactor-adjusted HR among women in the highest versus the lowest octile of CRP was 2.51 (1.53 to 4.12). Compared to women with CRP levels in the 0 to 25% percentile (<0.78 mg/L), the multifactor-adjusted HR of reduced overall survival among women with CRP levels ≥95% percentile (≥16.4 mg/L) was 3.58 (2.36 to 5.42). Among women with HER2-positive tumours, the multifactor-adjusted HR of reduced overall survival for the highest versus the lowest tertile of CRP was 8.63 (2.04 to 36.4).
Elevated CRP levels at the time of diagnosis of breast cancer are associated with reduced overall and disease-free survival and with increased risk of death from breast cancer.
An aberrant composition of the salivary microbiota has been found in individuals with type 2 diabetes, and in pregnant women salivary microbiota composition has been associated with preeclampsia and ...pre-term birth. Pregnant women, who develop gestational diabetes (GDM), have a high risk of developing type 2 diabetes after pregnancy. In the present study we assessed whether GDM is linked to variation in the oral microbial community by examining the diversity and composition of the salivary microbiota.
In this observational study the salivary microbiota of pregnant women with GDM (n = 50) and normal glucose regulation (n = 160) in third trimester and 9 months postpartum was assessed by 16S rRNA gene amplicon sequencing of the V1-V3 region. GDM was diagnosed in accordance with the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. Cross-sectional difference in alpha diversity was assessed using Student's t-test and longitudinal changes were assessed by mixed linear regression. Cross-sectional and longitudinal difference in beta diversity was assessed by permutational multivariate analyses of variance. Differentially abundant genera and OTUs were identified by negative binomial regression.
In the third trimester, two species-level operational taxonomic units (OTUs), while eight OTUs postpartum were differentially abundant in women with GDM compared with normoglycaemic women. OTU richness, Shannon diversity and Pielou evenness decreased from late pregnancy to 9 months after delivery regardless of glycaemic status.
GDM is associated with a minor aberration of the salivary microbiota during late pregnancy and postpartum. For unknown reasons richness of the salivary microbiota decreased from late pregnancy to postpartum, which might be explained by the physiological changes of the immune system during human pregnancy.
Summary
Background
Appendicitis is a common disease with a lifespan risk of approximately 8%. The full range of specific causes for the disease remains elusive, but an aberrant microbiota have been ...identified as a potential risk factor.
Aim
To investigate if use of antibiotics in a paediatric population increases the risk of appendicitis in childhood and adolescence
Methods
We conducted a cohort study from 1 January 1995 to 31 December 2014. A total of 1 385 707 children (0‐19 years of age) including 7 406 397 antibiotic prescriptions and 11 861 cases of appendicitis were included. Primary outcome was appendicitis requiring appendectomy according to previous use of antibiotics. Appendicitis and appendectomy were identified from nationwide hospital records, and exposure to antibiotics was identified from nationwide prescription register. Rate ratios (RRs) with 95% confidence intervals were estimated from Poisson and logistic regression models.
Results
Children who received at least one course of antibiotics were at increased risk of developing appendicitis compared to unexposed children (adjusted RR 1.72 95% confidence interval 1.61‐1.85), mean age of developing appendicitis was 9.8 years (SD 4.1 years). The RR of appendicitis increased by 1.04 (1.04‐1.04) per antibiotic course. A higher risk of appendicitis was observed in children exposed to antibiotics within the first 6 months of life (RR 1.46 1.36‐1.56) and children exposed to broad‐spectrum antibiotics (RR 1.33 1.27‐1.39). After adjustment for number of antibiotic courses, the association between early age of antibiotic exposure and risk of appendicitis and the association between exposure to broad‐spectrum antibiotics and the risk of appendicitis both disappeared.
Conclusion
Children who receive antibiotics are at increased and dose‐dependent risk of appendicitis. The underlying mechanisms merit further investigation.
Summary
Background
Escalation to anti‐tumour necrosis factor (anti‐TNF) in inflammatory bowel disease (IBD) patients on thiopurine is a common clinical scenario. However, the impact of discontinuing ...thiopurine at escalation is unclear.
Aim
To assess the impact of discontinuing versus continuing thiopurine therapy at anti‐TNF initiation.
Methods
We used the Danish registries to establish a national cohort of patients with IBD on thiopurine therapy prior to initiating anti‐TNF from 2003 to 2018. We compared patients discontinuing thiopurine therapy within 90 days of anti‐TNF initiation to those continuing. Our primary outcome was a composite of any new oral corticosteroid use, IBD‐related hospitalization, surgery or death. We used Cox regression models to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI).
Results
Of the 10,352 anti‐TNF exposed patients, 2,630 (1590 Crohn's disease (CD) and 1040 ulcerative colitis (UC)) received thiopurines prior to anti‐TNF. After anti‐TNF initiation, 979 patients discontinued thiopurines. Discontinuing thiopurines within 90 days of anti‐TNF initiation, increased the risk of the primary outcome (aHR: 1.22; 95% CI: 1.10‐1.36), particularly for IBD‐related hospitalization (aHR: 1.14; 95% CI: 1.00‐1.31) and oral corticosteroid use (aHR: 1.27; 95% CI: 1.13‐1.44). This increased risk of the primary outcome was seen in both CD (aHR: 1.17; 95% CI 1.02‐1.34) and UC (aHR: 1.32; 95% CI: 1.12‐1.55).
Conclusions
In a nationwide cohort study of IBD patients, we observed that discontinuing thiopurines after anti‐TNF initiation was associated with an increased risk of adverse outcomes, in particular an increase in hospitalizations. Further interventional studies exploring this common clinical scenario are required.
Continuing thiopurine therapy at the time of anti‐TNF initiation (versus discontinuing thiopurine) decreased the risk of adverse outcomes, including new corticosteroid use, IBD‐related hospitalization, IBD‐related surgery, and death in this nationwide cohort study of 2,630 patients with IBD. Particularly, it reduced hospitalization and new corticosteroid use, key goals in the management of IBD.
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