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      The impact of cesarean section on offspring overweight and obesity: a systematic review and meta-analysis

      , ,
      International Journal of Obesity
      Springer Science and Business Media LLC

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          Abstract

          Studies have reported inconsistent results concerning the association of cesarean section with offspring obesity. We performed a systematic review and meta-analysis to examine whether cesarean section increases the risk of later overweight and obesity. Pubmed, Embase and Web of Science were searched using different combinations of two groups of keywords: 'cesarean' and 'overweight/obesity'. Cohort or case-control studies that reported the association of cesarean section with childhood (3-8 years), adolescence (9-18 years) and/or adult (>19 years) overweight/obesity were eligible. Where possible, adjusted risk estimates were pooled using a random effects model; otherwise unadjusted estimates were pooled. Statistical heterogeneity was assessed with I(2) statistics; the values of 25%, 50% and 75% were considered to indicate low, medium and high heterogeneity, respectively. We conducted a subgroup analysis to identify the sources of heterogeneity according to study quality defined on the basis of the Newcastle-Ottawa Scale. In total, two case-control and seven cohort studies were identified for the literature review and 15 separate risk estimates were included in the meta-analysis. The overall pooled odds ratio (OR) of overweight/obesity for offspring delivered by cesarean section compared with those born vaginally was 1.33 (95% confidence interval (CI) 1.19, 1.48; I(2)=63%); the OR was 1.32 (1.15, 1.51) for children, 1.24 (1.00, 1.54) for adolescents and 1.50 (1.02, 2.20) for adults. In subgroup analysis, the overall pooled OR was 1.18 (1.09, 1.27; I(2)=29%) for high-quality studies and 1.78 (1.43, 2.22; I(2)=24%) for medium-quality (P for interaction=0.0005); no low-quality studies were identified. The ORs for children, adolescents and adults all tended to be lower for high-quality studies compared with medium-quality studies. Our results indicated that cesarean section was moderately associated with offspring overweight and obesity. This finding has public health implications, given the increase in cesarean births in many countries.

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          Childhood overweight after establishment of the gut microbiota: the role of delivery mode, pre-pregnancy weight and early administration of antibiotics.

          To investigate whether delivery mode (vaginal versus by caesarean section), maternal pre-pregnancy body mass index (BMI) and early exposure to antibiotics (<6 months of age) influence child's risk of overweight at age 7 years, hence supporting the hypotheses that environmental factors influencing the establishment and diversity of the gut microbiota are associated with later risk of overweight. Longitudinal, prospective study with measure of exposures in infancy and follow-up at age 7 years. A total of 28 354 mother-child dyads from the Danish National Birth Cohort, with information on maternal pre-pregnancy BMI, delivery mode and antibiotic administration in infancy, were assessed. Logistic regression analyses were performed with childhood height and weight at the 7-year follow-up as outcome measures. Delivery mode was not significantly associated with childhood overweight (odds ratio (OR):1.18, 95% confidence interval (CI): 0.95-1.47). Antibiotics during the first 6 months of life led to increased risk of overweight among children of normal weight mothers (OR: 1.54, 95% CI: 1.09-2.17) and a decreased risk of overweight among children of overweight mothers (OR: 0.54, 95% CI: 0.30-0.98). The same tendency was observed among children of obese mothers (OR: 0.85, 95% CI: 0.41-1.76). The present cohort study revealed that a combination of early exposures, including delivery mode, maternal pre-pregnancy BMI and antibiotics in infancy, influences the risk of overweight in later childhood. This effect may potentially be explained by an impact on establishment and diversity of the microbiota.
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            Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus: a meta-analysis of observational studies.

            The aim of this study was to investigate the evidence of an increased risk of childhood-onset type 1 diabetes in children born by Caesarean section by systematically reviewing the published literature and performing a meta-analysis with adjustment for recognised confounders. After MEDLINE, Web of Science and EMBASE searches, crude ORs and 95% CIs for type 1 diabetes in children born by Caesarean section were calculated from the data reported in each study. Authors were contacted to facilitate adjustments for potential confounders, either by supplying raw data or calculating adjusted estimates. Meta-analysis techniques were then used to derive combined ORs and to investigate heterogeneity between studies. Twenty studies were identified. Overall, there was a significant increase in the risk of type 1 diabetes in children born by Caesarean section (OR 1.23, 95% CI 1.15-1.32, p < 0.001). There was little evidence of heterogeneity between studies (p = 0.54). Seventeen authors provided raw data or adjusted estimates to facilitate adjustments for potential confounders. In these studies, there was evidence of an increase in diabetes risk with greater birthweight, shorter gestation and greater maternal age. The increased risk of type 1 diabetes after Caesarean section was little altered after adjustment for gestational age, birth weight, maternal age, birth order, breast-feeding and maternal diabetes (adjusted OR 1.19, 95% CI 1.04-1.36, p = 0.01). This analysis demonstrates a 20% increase in the risk of childhood-onset type 1 diabetes after Caesarean section delivery that cannot be explained by known confounders.
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              Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk.

              Compelling evidence supports the concepts that gut microbiota actively promotes weight gain and fat accumulation and sustains, indirectly, a condition of low-grade inflammation, thus enhancing the cardiovascular risk. Fewer Bacteroidetes and more Firmicutes seem to characterize the gut microbiota of obese people as compared with that of lean individuals. This difference translates into an increased efficiency of microbiota of obese individuals in harvesting energy from otherwise indigestible carbohydrates. Furthermore, the microbiota also seems able to favor fat accumulation. Indeed, studies performed in germ-free animals have demonstrated that conventionalization of sterile intestine with gut microbiota is associated with an enhanced expression of various lipogenic genes in different tissues, i.e., hepatic, adipose, and muscle tissues. Finally, the microbiota favors systemic exposure to the lipopolysaccharides (LPSs), large glycolipids derived from the outer membrane of Gram-negative bacteria. LPSs can cause a condition of "metabolic endotoxemia" characterized by low-grade inflammation, insulin resistance, and augmented cardiovascular risk. LPSs are a powerful trigger for the innate immune system response. Upon binding to the Toll-like receptor 4 and its coreceptors, LPSs trigger a cascade of responses ultimately resulting in the release of proinflammatory molecules that interfere with modulation of glucose and insulin metabolism, promote development and rupture of the atherosclerotic plaque, and favor progression of fatty liver disease to steatohepatitis. This review gives a comprehensive breakdown of the interaction among gut microbiota, LPSs, and the innate immune system in the development of obesity and promotion of an individual's cardiovascular risk.
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                Author and article information

                Journal
                International Journal of Obesity
                Int J Obes
                Springer Science and Business Media LLC
                0307-0565
                1476-5497
                July 2013
                December 4 2012
                July 2013
                : 37
                : 7
                : 893-899
                Article
                10.1038/ijo.2012.195
                23207407
                14fdc756-9e6d-4e44-8cba-a9d8875bab38
                © 2013

                http://www.springer.com/tdm


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