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- Koletzko, Sibylle, et al.
(author)
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Caesarean Section on The Risk of Celiac Disease in the Offspring : The Teddy Study
- 2018
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In: Journal of Pediatric Gastroenterology and Nutrition. - 0277-2116. ; 66:3, s. 417-424
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Journal article (peer-reviewed)abstract
- OBJECTIVE:: Caesarean section (C-section) is associated with various immune-mediated diseases in the offspring. We investigated the relationship between mode of delivery and celiac disease (CD) and CD autoimmunity (CDA) in a multinational birth cohort. METHODS:: From 2004 to 2010 infants from the general population who tested positive for HLA DR3-DQ2 or DR4-DQ8 were enrolled in The Environmental Determinants for Diabetes in the Young (TEDDY) study. Children were annually screened for transglutaminase autoantibodies, if positive re-tested after 3–6 months and those persistently positive defined as CDA. Associations of C-section with maternal (age, education level, parity, pre-pregnancy weight, diabetes, smoking, weight gain during pregnancy) and child characteristics (gestational age, birth weight) were examined by Fisherʼs exact test or Wilcoxon rank-sum test. Hazard ratios (HRs) for CDA or CD were calculated by Cox proportional hazard regression models. RESULTS:: Of 6,087 analyzed singletons 1600 (26%) were born by C-section (Germany 38%, US 37%, Finland 18%, Sweden 16%), the remaining vaginally without instrumental support; 979 (16%) had developed CDA and 343 (6%) CD. C-section was associated with lower risk for CDA (HR?=?0.85, [95% CI 0.73, 0.99], p?=?0.032) and CD (HR?=?0.75, [95% CI 0.58, 0.98], p?=?0.034). After adjusting for country, sex, HLA-genotype, CD in family, maternal education and breastfeeding duration, significance was lost for CDA (HR?=?0.91, [95% CI 0.78, 1.06], p?=?0.20) and CD (HR?=?0.85, [95% CI 0.65, 1.11], p?=?0.24). Pre-surgical ruptured membranes had no influence on CDA or CD development. CONCLUSION:: C-section is not associated with increased risk for CDA or CD in the offspring.
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| 2. |
- Stewart, Christopher J., et al.
(author)
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Temporal development of the gut microbiome in early childhood from the TEDDY study
- 2018
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 562:7728, s. 583-588
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Journal article (peer-reviewed)abstract
- The development of the microbiome from infancy to childhood is dependent on a range of factors, with microbial–immune crosstalk during this time thought to be involved in the pathobiology of later life diseases1–9 such as persistent islet autoimmunity and type 1 diabetes10–12. However, to our knowledge, no studies have performed extensive characterization of the microbiome in early life in a large, multi-centre population. Here we analyse longitudinal stool samples from 903 children between 3 and 46 months of age by 16S rRNA gene sequencing (n = 12,005) and metagenomic sequencing (n = 10,867), as part of the The Environmental Determinants of Diabetes in the Young (TEDDY) study. We show that the developing gut microbiome undergoes three distinct phases of microbiome progression: a developmental phase (months 3–14), a transitional phase (months 15–30), and a stable phase (months 31–46). Receipt of breast milk, either exclusive or partial, was the most significant factor associated with the microbiome structure. Breastfeeding was associated with higher levels of Bifidobacterium species (B. breve and B. bifidum), and the cessation of breast milk resulted in faster maturation of the gut microbiome, as marked by the phylum Firmicutes. Birth mode was also significantly associated with the microbiome during the developmental phase, driven by higher levels of Bacteroides species (particularly B. fragilis) in infants delivered vaginally. Bacteroides was also associated with increased gut diversity and faster maturation, regardless of the birth mode. Environmental factors including geographical location and household exposures (such as siblings and furry pets) also represented important covariates. A nested case–control analysis revealed subtle associations between microbial taxonomy and the development of islet autoimmunity or type 1 diabetes. These data determine the structural and functional assembly of the microbiome in early life and provide a foundation for targeted mechanistic investigation into the consequences of microbial–immune crosstalk for long-term health.
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