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.