Discussion
In this study, no associations were found between cesarean delivery and the development of asthma, atopic dermatitis, wheezing, and eczema among infants at 1 year of age. Moreover, patients delivered through elective and emergency cesarean deliveries had no increased risk of asthma, atopic dermatitis, wheezing, and eczema after adjusting for perinatal, socioeconomic, and postnatal confounding factors. Numerous studies have investigated the associations between cesarean delivery and allergic diseases, but the results have been inconsistent. The findings from a previous meta-analysis that included 15 cohort studies, four case-control studies, and one cross-sectional study, showed an association between cesarean delivery and asthma, and an increased risk of asthma among children born by cesarean delivery (OR = 1.20; 95% CI, 1.14–1.26).7Moreover, the authors of a meta-analysis that included 23 cohort studies and three case-control studies concluded that allergic outcomes were attributable to cesarean delivery in only 1–4% of subjects.8 In contrast, a population-based cohort study in the UK in 2004 showed that cesarean delivery was not associated with the subsequent development of physician-diagnosed asthma, wheezing, or atopy in later childhood (aOR = 1.14; 95% CI, 0.9–1.4; aOR = 0.95; 95% CI, 0.7–1.3]; and aOR = 1.04; 95% CI, 0.8–1.3, respectively).13 A population-based cohort study in the USA in 2005 showed that the mode of delivery was not associated with subsequent risk of developing childhood asthma (adjusted hazard ratio: 0.93; 95% CI, 0.6–1.4) or wheezing episodes (adjusted hazard ratio: 0.93; 95% CI, 0.7–1.3).14 A recent cohort study in Taiwan in 2017 showed that asthma was not associated with cesarean delivery after controlling for GA and parental history of asthma (aOR = 1.11; 95% CI, 0.98–1.25).15 Previous studies examining delivery by cesarean section and the development of infectious diseases had variable sample sizes, age groups, follow-up times, case definitions, and adjustments for confounding factors. However, this study is the largest pregnancy cohort study in which the association between cesarean delivery and asthma, atopic dermatitis, wheezing, and eczema among infants at 1 year of age was assessed while controlling for a wide range of influencing factors.
Children born by cesarean delivery show delays and differences in relation to the establishment of their gut flora, as well as altered cytokine profiles.10-12 Infants born by cesarean delivery acquire a microbiota that differs from that in infants delivered vaginally. While infants delivered vaginally harbor bacterial communities that resemble those of their mothers’ vaginas, infants born by cesarean delivery are enriched with skin microbiota.10, 11 Hence, the delivery mode may be a crucial factor that influences the development of an infant’s immune system and subsequent incidence of disease. Altered perinatal toll-like receptor responses and aberrant changes in cord blood cytokine responses, including those associated with interleukin (IL)-6, IL-8, IL-10, IL-13, tumor necrosis factor-α, and interferon-γ, are related to asthma, and neonates with bacterial colonization of the airways are at an increased risk of developing recurrent wheezing and asthma in early life.12 Another mechanism may be changes in the stress hormone levels at birth between cesarean and vaginal deliveries because infants delivered by cesarean section before the onset of labor lack the normal surge of stress hormones.22 These mechanisms may affect elective cesarean deliveries more than emergency cesarean deliveries because emergency cesarean deliveries often occur after the onset of labor, potentially resulting in exposure to the vaginal microflora and both maternal and fetal stress.22Children born by cesarean delivery, especially elective cesarean delivery, may have an increased risk of developing allergic diseases. However, the results from our study do not support this hypothesis. Based on recent evidence of the presence of bacteria in the placenta, amniotic fluid, and meconium, some investigators posit that the microbiome may be seeded before birth.23 These findings support the results from our study that showed there were no associations between cesarean delivery and the development of allergic diseases. Interestingly, in this study, emergency cesarean delivery reduced the development of eczema. However, this mechanism is unclear.
The strengths of our study include the prospective and nationwide design; the comparison of maternal questionnaires and medical records with birth certificates to verify the main exposure variable and other covariates; and use of prospectively collected data on asthma, atopic dermatitis, wheezing, and eczema. Multiple regression analysis was performed to correct for perinatal, socioeconomic, and postnatal factors.
However, this study has several limitations. First, we evaluated allergic diseases at 1 year of age using participants’ self-reported questionnaires, which may have led to the under-reporting of allergic diseases. Second, many infants may not be diagnosed with allergic diseases at 1 year of age because the diagnostic criteria for allergic diseases at this age are not clear. Finally, cesarean delivery may not have been strictly assigned to the elective or emergency cesarean delivery group in the JECS data; however, emergency cesarean delivery may have also included elective cesarean delivery. Most elective cesarean deliveries assigned in this study occurred before the onset of labor and exposure to vaginal flora. Despite these limitations, our study evaluated data from a large, nationwide, prospective birth cohort study, and therefore, provides strong evidence against an association between cesarean delivery and allergic diseases. This may have important clinical and public health implications. If cesarean delivery has clinical benefits, it should not be avoided because of the risk of allergic diseases in infants.