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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    • "Microbiome disturbances caused by antibiotic treatment during fi rst year of life may predispose to asthma (Droste et al. 2000 ; Murk et al. 2011 ). Furthermore, infants born by caesarean section and thereby not exposed to the mother's gut microbiome) are 20 % more likely to develop asthma (Thavagnanam et al. 2008 ). The specifi c intestinal microbiome composition that is related to allergic asthma has not been well defi ned. "
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    • "As many of these diseases start early in life, changes in gut flora composition may be secondary to neonatal environmental factors such as infant diet, medication, and mode of delivery. Interestingly, an increase in childhood allergies and asthma may be related to a parallel increase in caesarean sections, which have also been associated with coeliac disease and obesity868788. Moreover, many of the pathophysiological effects of microbiota disturbance, including altered immune function and metabolic consequences such as mitochondrial dysfunction, are shared between neurodevelopmental and age-related neurodegenerative conditions. "

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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.
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