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Cesarean section and interferon-induced helicase gene polymorphisms combine to increase childhood type 1 diabetes risk.

ABSTRACT: The incidence of type 1 diabetes is increasing. Delivery by cesarean section is also more prevalent, and it is suggested that cesarean section is associated with type 1 diabetes risk. We examine associations between cesarean delivery, islet autoimmunity and type 1 diabetes, and genes involved in type 1 diabetes susceptibility.Cesarean section was examined as a risk factor in 1,650 children born to a parent with type 1 diabetes and followed from birth for the development of islet autoantibodies and type 1 diabetes.Children delivered by cesarean section (n = 495) had more than twofold higher risk for type 1 diabetes than children born by vaginal delivery (hazard ratio [HR] 2.5; 95% CI 1.4-4.3; P = 0.001). Cesarean section did not increase the risk for islet autoantibodies (P = 0.6) but was associated with a faster progression to diabetes after the appearance of autoimmunity (P = 0.015). Cesarean section-associated risk was independent of potential confounder variables (adjusted HR 2.7;1.5-5.0; P = 0.001) and observed in children with and without high-risk HLA genotypes. Interestingly, cesarean section appeared to interact with immune response genes, including CD25 and in particular the interferon-induced helicase 1 gene, where increased risk for type 1 diabetes was only seen in children who were delivered by cesarean section and had type 1 diabetes-susceptible IFIH1 genotypes (12-year risk, 9.1 vs. <3% for all other combinations; P < 0.0001).These findings suggest that type 1 diabetes risk modification by cesarean section may be linked to viral responses in the preclinical autoantibody-positive disease phase.

SUBMITTER: Bonifacio E

PROVIDER: S-EPMC3219940 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Cesarean section and interferon-induced helicase gene polymorphisms combine to increase childhood type 1 diabetes risk.

Bonifacio Ezio E Warncke Katharina K Winkler Christiane C Wallner Maike M Ziegler Anette-G AG

Diabetes 20111201 12

<h4>Objective</h4>The incidence of type 1 diabetes is increasing. Delivery by cesarean section is also more prevalent, and it is suggested that cesarean section is associated with type 1 diabetes risk. We examine associations between cesarean delivery, islet autoimmunity and type 1 diabetes, and genes involved in type 1 diabetes susceptibility.<h4>Research design and methods</h4>Cesarean section was examined as a risk factor in 1,650 children born to a parent with type 1 diabetes and followed fr ...[more]

PMID: 22110093

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Project description:BackgroundGlobal cesarean section (CS) rates range from 1% to 52%, with a previous CS being the commonest indication. Labour following a previous CS carries risk of scar rupture, with potential for offspring hypoxic brain injury, leading to high rates of repeat elective CS. However, the effect of delivery by CS on long-term outcomes in children is unclear. Increasing evidence suggests that in avoiding exposure to maternal bowel flora during labour or vaginal birth, offspring delivered by CS may be adversely affected in terms of energy uptake from the gut and immune development, increasing obesity and asthma risks, respectively. This study aimed to address the evidence gap on long-term childhood outcomes following repeat CS by comparing adverse childhood health outcomes after (1) planned repeat CS and (2) unscheduled repeat CS with those that follow vaginal birth after CS (VBAC).Methods and findingsA data-linkage cohort study was performed. All second-born, term, singleton offspring delivered between 1 January 1993 and 31 December 2007 in Scotland, UK, to women with a history of CS (n = 40,145) were followed up until 31 January 2015. Outcomes assessed included obesity at age 5 y, hospitalisation with asthma, learning disability, cerebral palsy, and death. Cox regression and binary logistic regression were used as appropriate to compare outcomes following planned repeat CS (n = 17,919) and unscheduled repeat CS (n = 8,847) with those following VBAC (n = 13,379). Risk of hospitalisation with asthma was greater following both unscheduled repeat CS (3.7% versus 3.3%, adjusted hazard ratio [HR] 1.18, 95% CI 1.05-1.33) and planned repeat CS (3.6% versus 3.3%, adjusted HR 1.24, 95% CI 1.09-1.42) compared with VBAC. Learning disability and death were more common following unscheduled repeat CS compared with VBAC (3.7% versus 2.3%, adjusted odds ratio 1.64, 95% CI 1.17-2.29, and 0.5% versus 0.4%, adjusted HR 1.50, 95% CI 1.00-2.25, respectively). Risk of obesity at age 5 y and risk of cerebral palsy were similar between planned repeat CS or unscheduled repeat CS and VBAC. Study limitations include the risk that women undergoing an unscheduled CS had intended to have a planned CS, and lack of data on indication for CS, which may confound the findings.ConclusionsBirth by repeat CS, whether planned or unscheduled, was associated with an increased risk of hospitalisation with asthma but no difference in risk of obesity at age 5 y. Greater risk of death and learning disability following unscheduled repeat CS compared to VBAC may reflect complications during labour. Further research, including meta-analyses of studies of rarer outcomes (e.g., cerebral palsy), are needed to confirm whether such risks are similar between delivery groups.

Project description:BACKGROUND:In Denmark, the cesarean section rate has increased by 49% between 1998 and 2015 and accounts for 21% of all births. Cesarean sections may cause short- as well as long-term consequences for both the mother and the child and impose further risks in future pregnancies. Delaying pregnancy until advanced maternal age at childbirth has been suggested as contributing to the increase. The proportion of women giving birth at 35 years or above increased from 15% (1998) to 21% (2015). Advanced maternal age at childbirth has been found to be related to increased pre-pregnancy morbidity and associated risk factors that may contribute to an increased risk of cesarean section. The aim of this study was to examine the association between advanced maternal age and cesarean section in a Danish population and the influence of demographic, anthropometric, health, and obstetric factors on this association. METHODS:This study draws on a national population-based cohort study of all Danish births between 1998 and 2015 (N = 1,122,964). Maternal age less than 30 years serves as reference with the following age categories: (30-34 years); (35-39 years), and (40 years and above). The primary outcome was a cesarean section. Multivariate regression models with adjustment for demographic, health, pregnancy, fetal, and obstetric characteristics were performed with the results further stratified by parity. RESULTS:In general, a positive association between advanced maternal age and cesarean section was found. Only minor changes in the risk estimate occurred after adjustment for relevant confounders. In comparison with the reference category, nulliparous women aged 35-39- years had twice the risk for cesarean section (adjusted odds ratio (AOR) 2.18, 95% confidence interval (CI) [2.11-2.26]) whereas for women of 40 years or above, the risk was more than tripled (AOR 3.64, 95% CI [3.41-3.90]). For multiparous women aged 35-39-years the risk was more moderate, but still with an AOR of 1.56, 95% CI [1.53-1.60], and for those 40 years and above, the AOR was 2.02, 95% CI [1.92-2.09]. CONCLUSIONS:Overall, cesarean section increased with increasing maternal age. Adjustment for maternal and obstetric risk factors had only a minor influence on the association. The association was stronger in nulliparous women compared to multiparous women. Given the lack of impact of demographic and health risks on the relationship between maternal age and cesarean section, the authors suggest obstetric culture could be added to the list of risk factors for a cesarean. Future research on obstetric culture is recommended as are studies on a possible age-related decrease in the ability to maintain the progression of labor. TRIAL REGISTRATION:The study uses depersonalized register data and has been approved by the Danish Data Protection Agency (2015-41-4168).

Project description:BackgroundRising cesarean section (CS) rates are a major public health concern and cause worldwide debates. To propose and implement effective measures to reduce or increase CS rates where necessary requires an appropriate classification. Despite several existing CS classifications, there has not yet been a systematic review of these. This study aimed to 1) identify the main CS classifications used worldwide, 2) analyze advantages and deficiencies of each system.Methods and findingsThree electronic databases were searched for classifications published 1968-2008. Two reviewers independently assessed classifications using a form created based on items rated as important by international experts. Seven domains (ease, clarity, mutually exclusive categories, totally inclusive classification, prospective identification of categories, reproducibility, implementability) were assessed and graded. Classifications were tested in 12 hypothetical clinical case-scenarios. From a total of 2948 citations, 60 were selected for full-text evaluation and 27 classifications identified. Indications classifications present important limitations and their overall score ranged from 2-9 (maximum grade =14). Degree of urgency classifications also had several drawbacks (overall scores 6-9). Woman-based classifications performed best (scores 5-14). Other types of classifications require data not routinely collected and may not be relevant in all settings (scores 3-8).ConclusionsThis review and critical appraisal of CS classifications is a methodologically sound contribution to establish the basis for the appropriate monitoring and rational use of CS. Results suggest that women-based classifications in general, and Robson's classification, in particular, would be in the best position to fulfill current international and local needs and that efforts to develop an internationally applicable CS classification would be most appropriately placed in building upon this classification. The use of a single CS classification will facilitate auditing, analyzing and comparing CS rates across different settings and help to create and implement effective strategies specifically targeted to optimize CS rates where necessary.

Dataset Information

Cesarean section and interferon-induced helicase gene polymorphisms combine to increase childhood type 1 diabetes risk.

Publications

Cesarean section and interferon-induced helicase gene polymorphisms combine to increase childhood type 1 diabetes risk.

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