Abstract
BackgroundThe mechanisms for the association between birth by cesarean section and atopy and asthma are largely unknown.ObjectiveTo examine whether cesarean section results in neonatal secretion of cytokines that are associated with increased risk of atopy and/or asthma in childhood. To examine whether the association between mode of delivery and neonatal immune responses is explained by exposure to the maternal gut flora (a marker of the vaginal flora).MethodsCBMCs were isolated from 37 neonates at delivery, and secretion of IL-13, IFN-γ, and IL-10 (at baseline and after stimulation with antigens [dust mite and cat dander allergens, phytohemagglutinin, and lipopolysaccharide]) was quantified by ELISA. Total and specific microbes were quantified in maternal stool. The relation between mode of delivery and cord blood cytokines was examined by linear regression. The relation between maternal stool microbes and cord blood cytokines was examined by Spearman's correlation coefficients.ResultsCesarean section was associated with increased levels of IL-13 and IFN-γ. In multivariate analyses, cesarean section was associated with an increment of 79.4 pg/ml in secretion of IL-13 by CBMCs after stimulation with dust mite allergen (P < 0.001). Among children born by vaginal delivery, gram-positive anaerobes and total anaerobes in maternal stool were positively correlated with levels of IL-10, and gram-negative aerobic bacteria in maternal stool were negatively correlated with levels of IL-13 and IFN-γ.ConclusionCesarean section is associated with increased levels of IL-13 and IFN-γ, perhaps because of lack of labor and/or reduced exposure to specific microbes (e.g., gram-positive anaerobes) at birth.
Highlights
The mechanisms for the association between birth by cesarean section and atopy and asthma are largely unknown
Among children born by vaginal delivery, total anaerobes and gram-positive anaerobes in maternal stool were each associated with increased secretion of IL-10 by cord blood mononuclear cells (CBMCs) after stimulation with Fel d 1 and Der f 1
A relationship between labor and neonatal secretion of IL-13, IFN-γ, and IL-10 has not been shown, the stress of labor has been associated with decreased T lymphocytes and CD4+ helper T cells [25,26], and increased neutrophils [27,28], natural killer (NK) cells [26,28], TNF-α [29], and IL-6 [13,29] in cord blood
Summary
The mechanisms for the association between birth by cesarean section and atopy and asthma are largely unknown. Increased cord blood levels of IL-13 have been positively associated with atopy among children with a family history of atopy [9,10,11]. Less consistent, increased cord blood levels of IFN-γ have been associated with atopy among children with a family history of atopy [11,12]. In children at risk for atopy, increased neonatal levels of IL-10 have been associated with reduced risk of egg allergy[10] but increased risk of atopic dermatitis [11,12]. Among children unselected for family history, detectable neonatal IL-10 was associated with a reduced risk of asthma at age 6 years[13]
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