Dataset Information

Cesarean Section on the Risk of Celiac Disease in the Offspring: The Teddy Study.

ABSTRACT: OBJECTIVE:Cesarean 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, they are retested after 3 to 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 Fisher exact test or Wilcoxon rank-sum test. Hazard ratios (HRs) for CDA or CD were calculated by Cox proportional hazard regression models. RESULTS:Of 6087 analyzed singletons, 1600 (26%) were born by C-section (Germany 38%, United States 37%, Finland 18%, Sweden 16%), and the remaining were born vaginally without instrumental support; 979 (16%) had developed CDA and 343 (6%) developed CD. C-section was associated with lower risk for CDA (hazard ratio [HR]?=?0.85; 95% confidence interval [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 breast-feeding 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). Presurgical 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.

SUBMITTER: Koletzko S

PROVIDER: S-EPMC5787038 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Cesarean Section on the Risk of Celiac Disease in the Offspring: The Teddy Study.

Koletzko Sibylle S Lee Hye-Seung HS Beyerlein Andreas A Aronsson Carin A CA Hummel Michael M Liu Edwin E Simell Ville V Kurppa Kalle K Lernmark Åke Å Hagopian William W Rewers Marian M She Jin-Xiong JX Simell Olli O Toppari Jorma J Ziegler Anette-G AG Krischer Jeffrey J Agardh Daniel D

Journal of pediatric gastroenterology and nutrition 20180301 3

<h4>Objective</h4>Cesarean 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.<h4>Methods</h4>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 ...[more]

PMID: 28753178

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Project description:IntroductionChildren born by cesarean section (CS) are at a greater risk of inflammatory bowel disease (IBD). However, the mechanisms underlying the association are not yet well understood. Herein, we investigated the impact of CS delivery on colonic inflammation and mechanisms underlying these effects in offspring.MethodsCS mice model and dextran sulfate sodium (DSS)-induced colitis model were constructed and used to analyze the impact of CS on the development of colitis. Colonic tight junction markers and epithelium differentiation markers were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Levels of zonulin in serum were detected by enzyme-linked immunosorbent assay (ELISA). Immune cells in colon were analyzed by flow cytometry. Metabolic profiling between human vaginal delivery (VD) and CS AF were analyzed by using mass spectrometry. Transcriptome changes between VD AF- and CS AF-treated human intestine epithelial cells were analyzed by RNA-sequencing. A multi-omics approach that integrated transcriptomics with metabolomics to identify the pathways underlying colonic inflammation associated with delivery modes. Then, the identified pathways were confirmed by immunoblotting and ELISA.ResultsMice pups delivered by CS exhibited a defective intestinal homeostasis manifested by decreased expression of tight junction markers of ZO-1 and Occludin in the colons, increased levels of zonulin in serum and dysregulated expression of intestinal epithelium differentiation markers of Lysozyme, Mucin2, and Dipeptidyl peptidase-4. CS pups were more susceptible to DSS-induced colitis compared to VD pups. The proportion of macrophage, dendritic cells (DCs), and natural killer cells (NKs) in the colons were altered in an age-dependent manner compared with pups born naturally. The metabolites in AF differed between CS and VD cases, and the CS AF-induced differentially expressed genes (DEGs) were significantly enriched in pathways underlying IBD. Signal transducer and activator of transcription 3 (STAT3) signaling was downregulated in NCM460 intestinal epithelial cells by CS AF compared to VD AF and in colon of CS pups compared to VD pups. Deficiency in metabolites like vitamin D2 glucosiduronate in CS AF may attribute to the risk of inflammatory intestine through STAT3 signaling.ConclusionOur study provides a novel insight into the underlying mechanisms of CS-associated intestinal inflammation and potential prevention strategies.

Project description:OBJECTIVES:Tissue transglutaminase autoantibodies (tTGAs) represent the first evidence of celiac disease (CD) development. Associations of HLA-DR3-DQA1*05:01-DQB1*02:01 (i.e., DR3-DQ2) and, to a lesser extent, DR4-DQA1*03:01-DQB1*03:02 (i.e., DR4-DQ8) with the risk of CD differ by country, consistent with additional genetic heterogeneity that further refines risk. Therefore, we examined human leukocyte antigen (HLA) factors other than DR3-DQ2 for their contribution to developing tTGAs. METHODS:The Environmental Determinants of Diabetes in the Young (TEDDY) study enrolled 8,676 infants at an increased HLA-DR-DQ risk for type 1 diabetes and CD into a 15-year prospective surveillance follow-up. Of those followed up, 21% (n=1,813) carried DR3-DQ2/DR3-DQ2, 39% (n=3,359) carried DR3-DQ2/DR4-DQ8, 20% (n=1701) carried DR4-DQ8/DR4-DQ8, and 17% (n=1,493) carried DR4-DQ8/DQ4. Within TEDDY, a nested case-control design of 248 children with CD autoimmunity (CDA) and 248 matched control children were genotyped for HLA-B, -DRB3, -DRB4, -DPA1, and -DPB1 genes, and the entire cohort was genotyped for single-nucleotide polymorphisms (SNPs) using the Illumina ImmunoChip. CDA was defined as a positive tTGA test at two consecutive clinic visits, whereas matching in those with no evidence of tTGAs was based on the presence of HLA-DQ2, country, and sex. RESULTS:After adjustment for DR3-DQ2 and restriction to allele frequency (AF) ?5%, HLA-DPB1*04:01 was inversely associated with CDA by conditional logistic regression (AF=44%, odds ratio=0.71, 95% confidence interval (CI)=0.53-0.96, P=0.025). This association of time to CDA and HLA-DPB1*04:01 was replicated with statistical significance in the remainder of the cohort using imputation for specific HLA alleles based on SNP genotyping (hazard ratio=0.84, 95% CI=0.73-0.96, P=0.013). CONCLUSIONS:HLA-DPB1*04:01 may reduce the risk of tTGAs, an early marker of CD, among DR3-DQ2 children, confirming that additional variants in the HLA region influence the risk for CDA.

Project description:BACKGROUND:Previous studies have suggested that cesarean section (CS) is associated with offspring overweight and obesity. However, few studies have been able to differentiate between elective and nonelective CS, which may differ in their maternal risk profile and biological pathway. Therefore, we aimed to examine the association between differentiated forms of delivery with CS and risk of obesity in young adulthood. METHODS AND FINDINGS:Using Swedish population registers, a cohort of 97,291 males born between 1982 and 1987 were followed from birth until conscription (median 18 years of age) if they conscripted before 2006. At conscription, weight and height were measured and transformed to World Health Organization categories of body mass index (BMI). Maternal and infant data were obtained from the Medical Birth Register. Associations were evaluated using multinomial and linear regressions. Furthermore, a series of sensitivity analyses were conducted, including fixed-effects regressions to account for confounders shared between full brothers. The mothers of the conscripts were on average 28.5 (standard deviation 4.9) years old at delivery and had a prepregnancy BMI of 21.9 (standard deviation 3.0), and 41.5% of the conscripts had at least one parent with university-level education. Out of the 97,291 conscripts we observed, 4.9% were obese (BMI ? 30) at conscription. The prevalence of obesity varied slightly between vaginal delivery, elective CS, and nonelective CS (4.9%, 5.5%, and 5.6%, respectively), whereas BMI seemed to be consistent across modes of delivery. We found no evidence of an association between nonelective or elective CS and young adulthood obesity (relative risk ratio 0.96, confidence interval 95% 0.83-1.10, p = 0.532 and relative risk ratio 1.02, confidence interval 95% 0.88-1.18, p = 0.826, respectively) as compared with vaginal delivery after accounting for prepregnancy maternal BMI, maternal diabetes at delivery, maternal hypertension at delivery, maternal smoking, parity, parental education, maternal age at delivery, gestational age, birth weight standardized according to gestational age, and preeclampsia. We found no evidence of an association between any form of CS and overweight (BMI ? 25) as compared with vaginal delivery. Sibling analysis and several sensitivity analyses did not alter our findings. The main limitations of our study were that not all conscripts had available measures of anthropometry and/or important confounders (42% retained) and that our cohort only included a male population. CONCLUSIONS:We found no evidence of an association between elective or nonelective CS and young adulthood obesity in young male conscripts when accounting for maternal and prenatal factors. This suggests that there is no clinically relevant association between CS and the development of obesity. Further large-scale studies are warranted to examine the association between differentiated forms of CS and obesity in young adult offspring. TRIAL REGISTRATION:Registered as observational study at ClinicalTrials.gov Identifier: NCT03918044.

Project description:BackgroundUp to 40% of women gain excessive weight during pregnancy. Obesity complications and risks in parturient women undergoing cesarean section (CS) with different anesthetic methods remain unknown. This study aimed to assess the safety and risk of obese women undergoing CS delivery with various perioperative anesthetic methods.MethodsSeven hundred ninety parturient women underwent CS under general anesthesia (GA), intraspinal anesthesia including epidural anesthesia (EA) and combined spinal-epidural anesthesia (CSEA). They were divided into morbid (n = 255), severe (n = 274), and non-obesity (n = 261) groups. This study is registered with ClinicalTrials.gov (number NCT03002636).ResultBetween 2013 and 2016, 790 pregnant were assessed. Compared with the non-obesity group, there were significantly more fetal distress and higher body mass index (BMI) in the morbid obesity group (P = .0001 and P = .001, respectively). Significantly more patients showed preeclampsia, multifetation, amniotic fluid abnormality, and high bleeding amounts in the morbid obesity group compared with the non-obesity group (P = .0001, P = .048, P = .017, and P = .018, respectively); more patients were administered EA and GA compared with the non-obesity group (P = .0001 and P = .0001, respectively). More post-anesthesia care unit (PACU) patients were found in the severe obesity group no more than the non-obesity group. Significantly increased anesthesia puncture times for 5 > n ≥ 3 and n ≥ 5 were obtained in the morbid obesity group (P = .0001 and P = .0001, respectively), with more patients in the puncture sitting position, compared with the non-obesity group (P = .0001).ConclusionGA, EA, and CSEA are safe and effective in severely or morbidly obese patients. Morbidly obese parturient show increased likelihood for fetal distress, PACU, sitting position puncture, puncture difficulty, and other pregnancy complications. There were more anesthesia puncture times in morbidly obese patients.

Dataset Information

Cesarean Section on the Risk of Celiac Disease in the Offspring: The Teddy Study.

Publications

Cesarean Section on the Risk of Celiac Disease in the Offspring: The Teddy Study.

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