A Meta-Analysis of the Association between Caesarean Section and Childhood Asthma

Royal Belfast Hospital for Sick Children, Belfast, Northern Ireland.
Clinical & Experimental Allergy (Impact Factor: 4.77). 04/2008; 38(4):629-33. DOI: 10.1111/j.1365-2222.2007.02780.x
Source: PubMed


Children born by Caesarean section have modified intestinal bacterial colonization and consequently may have an increased risk of developing asthma under the hygiene hypothesis. The results of previous studies that have investigated the association between Caesarean section and asthma have been conflicting.
To review published literature and perform a meta-analysis summarizing the evidence in support of an association between children born by Caesarean section and asthma.
MEDLINE, Web Science, Google Scholar and PubMed were searched to identify relevant studies. Odds ratio (OR) and 95% confidence interval (CI) were calculated for each study from the reported prevalence of asthma in children born by Caesarean section and in control children. Meta-analysis was then used to derive a combined OR and test for heterogeneity in the findings between studies.
Twenty-three studies were identified. The overall meta-analysis revealed an increase in the risk of asthma in children delivered by Caesarean section (OR=1.22, 95% CI 1.14, 1.29). However, in this analysis, there was evidence of heterogeneity (I(2)=46%) that was statistically significant (P<0.001). Restricting the analysis to childhood studies, this heterogeneity was markedly decreased (I(2)=32%) and no longer attained statistical significance (P=0.08). In these studies, there was also evidence of an increase (P<0.001) in the risk of asthma after Caesarean section (OR=1.20, 95% CI 1.14, 12.6).
In this meta-analysis, we found a 20% increase in the subsequent risk of asthma in children who had been delivered by Caesarean section.

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    • "Prenatal and early postnatal exposures and events can affect the entire life course. As one example, cesarean birth has been associated with an increased likelihood of asthma and cardiovascular disease in children (Renz-Polster et al., 2005; Thavagnanam et al., 2008; Friedemann et al., 2012), hypertension in young adults (Horta et al., 2013), and obesity in both children and adults (Pei et al., 2014; Darmasseelane et al., 2014; Blustein et al., 2013; Mueller et al., 2014). While these associations are certainly multifactorial, differences in the gut microbiota could contribute. "
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    ABSTRACT: Cesarean birth is associated with altered composition of the neonate's microbiota and with increased risk for obesity and other diseases later in life. The mechanisms of these associations, and whether cesarean birth is associated with an altered adult microbiota, are unknown. In 1097 adult volunteers without diabetes, inflammatory bowel disease, or recent antibiotic use, fecal microbiome metrics were compared by history of cesarean birth (N=92) or appendectomy (N=115). Associations with potential confounders, microbiome alpha diversity, and individual microbial taxa were estimated by logistic regression. Permutation tests assessed differences in microbial composition (beta diversity) based on Jensen-Shannon divergence. Cesarean birth history was associated with younger age; appendectomy with older age and higher body mass index. Neither was associated with fecal microbiome alpha diversity. Microbial composition at all taxonomic levels differed significantly with cesarean birth (P≤0.008) but not with appendectomy (P≥0.29). Relative abundance differed nominally for 17 taxa with cesarean birth and for 22 taxa with appendectomy, none of which was significant with adjustment for multiple comparisons. Adults born by cesarean section appear to have a distinctly different composition of their fecal microbial population. Whether this distinction was acquired during birth, and whether it affects risk of disease during adulthood, are unknown.
    12/2014; 1(2-3):167-172. DOI:10.1016/j.ebiom.2014.11.004
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    • "Nevertheless, it appears that birth by Caesarean section delays transfer of additional maternal microbiota and alters the course of colonization (Dominguez-Bello et al., 2010). This might explain the observations that Caesarean birth increases the risk of allergy (Guibas et al., 2013; Magnus et al., 2011; Thavagnanam et al., 2008), autoimmunity (Bonifacio et al., 2011; Cardwell et al., 2008), and, to a more modest extent, both coeliac (Decker et al., 2010), and inflammatory bowel disease (Bager et al., 2012; Malmborg et al., 2012). A nice example of the importance of transfer of maternal microbiota comes from the observation that if the mother thoroughly washes and boils the baby's pacifier (dummy) after it has fallen on the floor, that baby has an increased risk of developing asthma, eczema or allergic sensitization compared to babies whose mothers merely suck the pacifier and put it back in the baby 0 s mouth (Hesselmar et al., 2013). "
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    ABSTRACT: The immune system influences brain development and function. Hygiene and other early childhood influences impact the subsequent function of the immune system during adulthood, with consequences for vulnerability to neurodevelopmental and psychiatric disorders. Inflammatory events during pregnancy can act directly to cause developmental problems in the central nervous system (CNS) that have been implicated in schizophrenia and autism. The immune system also acts indirectly by "farming" the intestinal microbiota, which then influences brain development and function via the multiple pathways that constitute the gut-brain axis. The gut microbiota also regulates the immune system. Regulation of the immune system is crucial because inflammatory states in pregnancy need to be limited, and throughout life inflammation needs to be terminated completely when not required; for example, persistently raised levels of background inflammation during adulthood (in the presence or absence of a clinically apparent inflammatory stimulus) correlate with an increased risk of depression. A number of factors in the perinatal period, notably immigration from rural low-income to rich developed settings, caesarean delivery, breastfeeding and antibiotic abuse have profound effects on the microbiota and on immunoregulation during early life that persist into adulthood. Many aspects of the modern western environment deprive the infant of the immunoregulatory organisms with which humans co-evolved, while encouraging exposure to non-immunoregulatory organisms, associated with more recently evolved "crowd" infections. Finally, there are complex interactions between perinatal psychosocial stressors, the microbiota, and the immune system that have significant additional effects on both physical and psychiatric wellbeing in subsequent adulthood.
    Brain research 04/2014; 1617. DOI:10.1016/j.brainres.2014.04.004 · 2.84 Impact Factor
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    • "These babies have less Bifidobacterium and Bacteroides species in the gut [68] [69] and are more prone to colonization by Clostridium difficile , a pathobiont associated with wheezing and atopy in children [66] [48]. A meta-analysis of 23 studies concluded that infants born via ceasarian section have a 20% increase in risk of developing asthma during childhood compared to vaginally delivered infants [70]. Among the many benefits already described for breastfeeding, it also appears to confer protection against atopy [71] [72] except when there is genetic predisposition to the disease [73] [74]. "
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    ABSTRACT: There currently is no consensus on which immunological mechanisms can best explain the rise in atopic disease post industrialization. The hygiene hypothesis lays groundwork for our understanding of how altered microbial exposures can drive atopy; yet since its introduction increasing evidence suggests the exposure of our immune system to the intestinal microbiota plays a key role in development of atopic disease. As societal change shifts our microbial exposure, concordant shifts in the tolerant and effector functions of our immune systems give rise to more hypersensitive responses to external antigens. This is contrasted with the greater immune tolerant capabilities of individuals still living in regions with lifestyles more representative of our evolutionary history. Recent findings, buoyed by technological advances in the field, suggest a direct role for the intestinal microbiota-immune system interplay in the development of atopic disease mechanisms. Overall, harnessing current mechanistic studies for translational research into microbiota composition and function in relation to atopy have potential for the design of therapeutics that could moderate these diseases.
    Seminars in Immunology 10/2013; 25(5). DOI:10.1016/j.smim.2013.09.003 · 5.17 Impact Factor
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